TSG101 has been identified as a candidate tumor suppressor gene and abnormal transcripts have been identified in a substantial fraction of breast cancers. To determine whether TSG101 expression is commonly altered in other tumors, a series of 15 primary and metastatic prostate cancers were analysed by reverse transcriptase-PCR amplification. Abnormal transcripts with extensive deletions in the coding region were found in nine of these tumors, while only the normal transcript was found in control and benign prostatic hypertrophy tissues. More than one abnormal transcript was found in four of these nine cases and distinct abnormal TSG101 transcripts were found in separate biopsies taken from one tumor. Importantly, the normal TSG101 transcript was undetectable in two metastatic prostate cancers, indicating the absence of TSG101 protein. Sequence analysis demonstrated that there were at least six distinct deletions, with four of these deletions found in more than one tumor sample. The most commonly identified deletion, from bp 153 to 1055, was identical to a deletion reported previously in breast cancer. These results demonstrate that TSG101 transcripts are frequently abnormal in prostate cancer and suggest that loss of TSG101 protein contributes to disease development or progression.