To investigate a potential role of NF2, the gene responsible for hereditary bilateral acoustic neurinomas, during carcinogenesis of non-neurogenic tissues, we screened somatic mutations of NF2 in 55 breast cancers and 44 colorectal carcinomas by an RNase protection assay coupled with the reverse-transcriptase polymerase chain reaction (RT-PCR). By screening the entire coding region of the gene in these tumors, we detected missense mutations in the exon encoding the alpha-helical domain of the NF2 product in two colorectal carcinomas. No mutations were detected in any of the breast cancers. Our results suggested that inactivation of the NF2 gene was associated with carcinogenesis in some, but not the majority of, colorectal tumors. In the course of these analyses, we found various alternatively-spliced forms of NF2 transcript. These variants showed no specificity among the tissues examined except for one that resulted from alternative splicing at the 3'-region; this form was more abundantly expressed in skeletal and cardiac muscles than in other tissues.