Not every medical condition or disease can be diagnosed right off the bat. And sometimes, one illness can masquerade as another.

When there is uncertainty in a diagnosis, primary care doctors may refer a patient to specialists to help figure out what’s going on—a “second opinion.” That can be time-consuming and expensive, so it’s important to know how often this practice actually makes a difference.

Surprisingly often, according to new research from the Mayo Clinic. In more than one-fifth of cases studied, what was actually wrong with a patient was dramatically different from the original provisional diagnosis.

Here’s why it matters: The wrong diagnosis can lead your doctor to start you on a treatment path that won’t help and may harm—while allowing your real illness to go untreated for too long. Read on to find out how often primary care doctors got their provisional diagnoses right, “almost” right or downright wrong—and what that means to you as a patient.

Background: In medicine, everything depends on the accuracy of the diagnosis. But getting it right the first time can be a challenge. What looks like irritable bowel syndrome actually may be the far more serious ulcerative colitis. Toenail fungus and psoriasis—and malignant melanoma—can have similar symptoms.

Many people think of second opinions as something patients seek when they doubt their doctors’ diagnoses. That does happen, but much of the time it’s the doctors themselves who reach out to other doctors for second opinions. That’s a good thing. Their honesty in saying “I’m not sure” can save lives. The cost, hassle and, in many cases, lack of cooperation by insurance companies, however, are among the factors that convinced researchers to try to find out just how often second opinions actually change a final diagnosis.

Study: Researchers from the Mayo Clinic in Rochester, Minnesota, reviewed the records of 286 patients who were referred to the clinic’s internal medicine division from community-based primary care practices for help in diagnosis. About two-thirds of the patients were 64 or younger and one-third 65 or older.

The researchers compared the initial diagnoses for those patients with their final diagnoses. They also calculated the costs associated with extra office visits, imaging and laboratory tests that were part of the second-opinion evaluations and initial treatments.

Results: The specialists’ diagnoses exactly matched the diagnoses of the primary care doctors in 12% of the cases. These particular second opinions cost, on average, $1,288 per patient—and didn’t change anything relating to treatment for these patients.

Two thirds of the time (66%), although the primary provisional diagnostic observations weren’t wrong, the specialists were needed to pinpoint the specific diagnoses that could lead to effective treatment. These second opinions cost a little more—on average $1,794 per patient. Examples…

  • Original uncertain diagnosis: Weakness. What was really going on: Medication-induced rhabdomyolysis (breakdown of muscle cells and release of contents into the blood).
  • Original uncertain diagnosis: Endocrine (hormone) abnormalities. What was really going on: The second-opinion docs found evidence of opioid-induced damage to the endocrine system that resulted in low production of steroid hormones.
  • Original uncertain diagnosis: Elevated PSA level and a spinal mass. What was really going on: Prostate cancer that had spread to the spine and lungs.

In 21% of the cases, however, the final diagnoses were very different from the original ones.  Examples…

Original uncertain diagnosis: Anemia. What was really going on: Autoimmune hepatitis.

Original uncertain diagnosis: Unintentional weight loss. What was really going on: Malignant lymphoma, most likely Hodgkin’s lymphoma.

Original uncertain diagnosis: Fatigue. What was really going on: Heart failure.

Not surprisingly, these second opinions that led to new diagnoses were expensive, costing on average $4,767 per patient.

Bottom line: This study doesn’t show that primary care doctors did anything wrong. In fact, they did something right—acknowledged that they weren’t sure what was going on and referred their patients for more specialized diagnoses. So if your doctor refers you to a specialist to figure out what’s really going on, follow through. And if you might be facing a serious illness, don’t hesitate to ask your primary care doctor about a second opinion—even if it means pushing back against your insurance company.