BACKGROUND The vascular system of the tumor bed plays an important function in tumor growth regulation. Recent studies have suggested that the vasoactive peptides somatostatin and substance P may have a potential role in the tumor bed of selected tumors. METHODS In the current study, somatostatin receptors were evaluated with in vitro receptor autoradiography using 125I‐Tyr3‐octreotide in the peritumoral vessels of a large group of 215 primary human tumors and 25 metastases of various tumor origin, with particular emphasis on receptor incidence, distribution, homogeneity, and density. RESULTS High affinity somatostatin receptors were found in the peritumoral veins of 22 of 22 gastric carcinomas, 25 of 39 breast carcinomas, 15 of 20 renal cell carcinomas, 14 of 27 prostate carcinomas, 4 of 10 endometrial carcinomas, 4 of 11 pancreatic adenocarcinomas, 4 of 13 nonsmall cell lung carcinomas, as well as in 3 of 4 parathyroid adenomas, 3 of 3 medullary thyroid carcinomas, 3 of 23 gastroenteropancreatic tumors, 14 of 25 soft tissue tumors, 3 of 5 melanomas but in none (0 of 13) of the ovarian carcinomas studied. In addition, somatostatin receptors were identified in veins surrounding lymph node, bone, and lung metastases of various tumor types. In all investigated tissues, receptors could not be identified in arteries. There was a considerable variability in the relative number of veins expressing somatostatin receptors and in the receptor density levels. Evidence of an overexpression of somatostatin receptors could be established in the peritumoral veins of gastric carcinoma when compared with the receptor expression in normal gastric vessels. CONCLUSIONS The expression of somatostatin receptors in peritumoral veins appears to be a general, tumor‐related, but highly variable phenomenon. Although their pathophysiologic role is unclear, these receptors may be considered as novel targets for cancer diagnosis and therapy with somatostatin analogs. Cancer 1999;85:188–98. © 1999 American Cancer Society. The vascular system of the tumor bed plays a crucial role in tumor growth regulation. The expression of receptors for the vasoactive peptide somatostatin in the veins of the tumor bed is observed in a wide variety of human malignancies, suggesting a possible role of somatostatin at this anatomic site.