Expression of the 67-kd laminin receptor (67-kd LR) has been reported in a wide range of carcinomas, in many of which it correlated with poor differentiation, metastasis, disease progression, and poor survival. Malignant mesothelioma (MM) is a locally aggressive and highly lethal tumor of serosal cavities that is rarely associated with clinically detectable metastasis to distant organs. The aim of this study was to analyze the expression of the 67-kd LR in epithelioid MM and carcinomas in effusions. Effusions from patients diagnosed with ovarian (=24) and breast (=38) adenocarcinomas and MM (=24) (total = 86) were analyzed for 67-kd LR protein expression, using immunocytochemistry. The 67-kd LR mRNA expression was additionally analyzed in 21 MM effusions using reverse transcription-polymerase chain reaction (RT-PCR). Protein expression of the 67-kd LR was frequently detected in carcinomas (19/24 ovarian tumors, 79%; 15/38 breast tumors, 39%), but was rare in MM (2/24 cases, 8%), despite the presence of mRNA transcripts for the receptor in all 21 specimens studied using RT-PCR. Nine benign effusions that were additionally studied for protein expression were uniformly negative, as were all reactive mesothelial cells in malignant effusions. Our results suggest that the 67-kd LR may aid in the differential diagnosis between metastatic carcinoma, mainly of ovarian origin, and MM. They additionally suggest that the failure of MM to express the 67-kd LR protein, as opposed to the frequent expression in carcinomas with proven metastatic capacity, may be one of the factors contributing to the reduced ability of the former tumor to metastasize to distant organs.