The pathologic diagnosis of hypertrophic cardiomyopathy (HCM) rests on the gross cardiac morphology and the presence and extent of myofiber disarray in the interventricular septum. Little attention, however, has been focused on the features of HCM in endomyocardial biopsy or septal myomectomy specimens. We therefore examined nine right ventricular biopsy specimens and 89 myomectomy specimens from 98 patients with clinically diagnosed HCM. Myofiber disarray was present in three (33%) of the biopsy specimens and 52 (58%) of the septectomy specimens. Associated findings in both specimen types included myocyte hypertrophy and interstitial fibrosis. The myomectomy specimens also frequently contained areas of patchy fibrosis, abnormally thick coronary arteries, and a fibrous endocardial plaque. When myofiber disarray was present in myomectomy specimens, it was confined to the deepest portion in 79% of the specimens, confirming that the disarray is frequently confined to the middle transverse third of the septum. Endomyocardial biopsy specimens may be used to suggest the diagnosis of HCM; however, because of their small size and their relatively nonspecific pathologic changes, they are of limited value in making the diagnosis of HCM. Septal myomectomy specimens usually contain pathologic findings consistent with HCM. The role of the surgical pathologist in the myomectomy cases is to confirm that these changes are present and are characteristic of the disorder.