Classical cytogenetic studies have a critical role in the diagnosis of acute leukemias; however, they are much less widely used in lymphoma diagnosis. To evaluate their utility in this latter setting, G-banded karyotyping was performed on 279 consecutive lymph node or tissue biopsy specimens with suspected lymphoma. Complete cytogenetic studies were successfully obtained in 177 cases (63.4%), including 115 (69.3%) of 166 hematolymphoid neoplasms. Success rates varied with the specific diagnosis (range, 33%-100%). The karyotypes were abnormal in 97 (84.3%) of the hematolymphoid neoplasms. In at least 3 cases of non-Hodgkin lymphoma, the findings contributed directly to the specific diagnosis made. In a much larger proportion of cases, characteristic but nonspecific findings were identified. Abnormalities of suggested prognostic importance in follicular lymphoma and in diffuse large B-cell lymphoma were identified in 14 (44%) of 32 cases and 8 (24%) of 33 cases, respectively. Most karyotyped lymphomas will display abnormal findings including many that are not completely specific but support the diagnosis, some that provide additional prognostic information, and, infrequently, some that help establish a diagnosis that might otherwise have been missed.