Long-term athletic training is associated with morphologic left ventricular (LV) remodeling, that in elite athletes may be substantial and raise differential diagnosis with structural heart disease, ie, hypertrophic cardiomyopathy (HCM). Several criteria for differential diagnosis are discussed here, including the morphologic features of LV hypertrophy in athletes (ie, the symmetric distribution of LV wall thickening, the enlarged cavity with normal shape) and normal diastolic LV filling pattern. The most definitive criterion for differential diagnosis is the response to deconditioning, which is associated with a substantial reduction in LV wall thickness (by 2-5 mm, mean 3 mm) in athlete's heart; no substantial morphologic changes occur in patients with HCM. Finally, genetic screening for DNA abnormalities, although at present limited to research-oriented genotyping of family HCM pedigrees and are not yet available for clinical purposes, in the near future may offer the most definitive diagnosis of HCM, regardless of the morphologic expression and clinical presentation of the disease.