There is little correlation between the clinical and the biopsy tissue diagnoses of myocarditis, and both are prone to false-positive and false-negative interpretations. Perhaps the most common error that leads to a false-positive clinical diagnosis of myocarditis is the preconceived but unproved notion that unexplained heart failure of sudden onset or rapid progression must be due to myocarditis. Therefore, most clinical diagnoses of myocarditis are presumptive and are never proved "beyond all reasonable doubt." False-negative clinical diagnoses may occur in patients with myocarditis in whom signs and symptoms are atypical or absent. The two most common sources of error that result in a false-positive biopsy tissue diagnosis of myocarditis are a failure to recognize how many lymphocytes normally occupy the myocardial interstitium and a misinterpretation of noninflammatory interstitial cells as lymphocytes. Sampling error may be the most common cause of false-negative tissue diagnoses in patients with myocarditis. Myocarditis is characterized histologically by an inflammatory infiltrate and by injury to myocardial cells that is not typical of infarction. Healing may occur by resolution or fibrosis. I believe that quantitative evidence of an interstitial leukocytic infiltrate is currently the best histopathologic criterion for the diagnosis of myocarditis in biopsy tissue. In the setting of clinically suspected myocarditis, the tissue diagnosis of myocarditis in a patient's first biopsy should be designated as present, borderline, or absent. In subsequent biopsies, the myocarditis should be evaluated in a temporal as well as a qualitative or quantitative sense and designated as ongoing, resolving, or resolved. The nature of the inflammatory infiltrate and the extent of fibrosis should also be stated in all such biopsies. The pathologist should render an evaluation that is as accurate and unbiased as possible, since patients with a tissue diagnosis of myocarditis often receive immunosuppressive therapy that may have associated morbidity or even mortality.