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Unknown primary tumors (UPT) are characterized by early and widespread metastasis. There is a strong indication that angiogenesis measured as microvessel density (MVD) correlates with the incidence of metastases in several solid tumors. The objective of this study was to compare MVD in liver metastases of UPT with MVD in known primaries and in liver metastases of colon and breast tumors and to investigate the pronostic significance of MVD in UPT. The clinical data and the MVD in liver metastases of 39 consecutive patients with UPT adenocarcinomas were studied. For comparison, MVD in the primary tumor and in liver metastases from known primary adenocarcinomas of the colon (n = 24) and the breast (n = 6) were measured. Most of the pathological material was obtained by needle biopsy. MVD was determined on formalin‐fixed, paraffin‐embedded histological sections of liver metastases, using the CD34 and von Willebrand Factor (vWF) antibodies and immunocytochemistry. The association of MVD with age, gender, number of metastases and tumor differentiation was assessed in the UPT population. The prognostic value of clinical variables and of MVD on survival was estimated by univariate and multivariate regression analysis. There was no difference between the MVD in liver metastases of UPT and known primaries. The MVD counts in the primary tumors of colon and breast were, however, significantly higher than in the metastases. MVD counts correlated well between anti‐CD34 and anti‐vWF. Within the UPT population there was no association between MVD and age, gender, number of metastases and tumor differentiation. The MVD was the only prognostic factor for survival in univariate analysis. High MVD was correlated with short survival. In the multivariate analysis, the number of metastases, tumor differentiation, therapy and MVD were all prognostic indicators for survival. Int. J. Cancer 74:81‐85. © 1997 Wiley‐Liss, Inc.