A wide variety of primary and metastatic human neoplasms express somatostatin receptors (SS-Rs). We evaluated the SS-R status of malignant lymphomas that had been surgically removed from 31 patients by use of in vitro SS-R autoradiography with the SS analog 125I-[Tyr3]-octreotide as radioligand. Of 11 low-grade-malignancy B-cell non-Hodgkin's lymphomas, 10 were SS-R-positive, with a high receptor density restricted to the neoplastic follicles. All of the 8 intermediate-grade lymphomas were SS-R-positive. Of the B-cell lymphomas of high-grade malignancy, 7 out of 10 were SS-R-positive, often with a high density of receptors. One T-cell lymphoma and one Hodgkin's lymphoma were also positive. SS-Rs were of high affinity (KD = 1.2 nM) and specific for bioactive SS analogs. In 4 patients, the lymphomas were localized in vivo by use of gamma-camera scintigraphy after i.v. injection of the SS analog 111In-[DTPA-D-Phe1]-octreotide. Hot spots, identified in all 4 patients, corresponded to SS-R-positive malignant-lymphoma tissue, as confirmed by receptor autoradiography of the surgically removed tumors. Our data show that SS-Rs are valuable pathobiochemical tissue markers and potentially useful in vivo diagnostic tools for human malignant lymphomas.