Inactivation of the TSG101 gene was recently shown to induce malignant transformation of NIH/3T3 fibroblasts. Abnormal TSG101 transcription profiles were observed in various human cancers, and large intragenic deletions of the TSG101 gene were reported for a series of human breast cancer specimens, pointing to a potential tumor-suppressive activity of TSG101. However, subsequent more detailed studies on a large panel of breast carcinoma samples did not confirm the tumor-associated genomic deletions. Here we analyzed the transcription patterns of the TSG101 gene in soft-tissue sarcomas and non-neoplastic human tissues. Forty-five of 71 soft tissue sarcoma samples (63%) displayed variant transcripts; however, identical aberrant transcripts were also detected in seven of 15 non-neoplastic control tissues. Restriction fragment length polymorphism analysis of the TSG101 gene excluded major genomic rearrangements in the soft tissue sarcoma samples. Northern blot analysis revealed a very low abundance of variant transcripts as compared with the wild-type TSG101 transcript. These data point to aberrant splicing of the TSG101 mRNA in normal and transformed human mesenchymal tissues rather than tumor specific alterations of the TSG101 gene. In summary, this analyses does not support a pathogenic role for altered TSG101 expression in human soft tissue sarcomas.