Somatic mutations of the adenomatous polyposis coli (APC) gene have been frequently found in sporadic colorectal tumors, and the frequency of such mutations remain constant as tumors progress from benign adenomas to malignant cancers. Thus the mutations of the APC gene may have a major role in the early development of sporadic colorectal tumors. Whether inactivation of the APC gene accounts for other types of primary tumors is still being investigated. We investigated for APC mutations within the mutation cluster region (a 684-bp region containing most of the mutations found in colorectal tumors) in 317 samples from a wide variety of human malignant and premalignant tissues, including 40 lung cancers, 47 renal cell carcinomas, 41 osteosarcomas and 21 other types of sarcomas, 45 acute lymphoid leukemias/lymphomas, 33 acute myeloid leukemias, 27 myelodysplastic syndrome samples, and 20 chronic colitis (ulcerative colitis and Crohn's disease) associated cancers and dysplasias, and 43 human malignant cell lines. We used single-strand conformation polymorphism assay following polymerase chain reaction. Samples with abnormal assay results were reamplified and analyzed by the direct DNA sequencing method. We detected a total of two cases with a base substitution. A silent mutation was detected in a case of myelodysplastic syndrome, and a novel nonsense mutation was discovered in a colorectal cancer cell line, SW837. In summary, we did not detect any functional mutations of the APC gene in a wide variety of tumors except for a colon cancer cell line, suggesting that alterations of the APC gene do not have a major role in the development of lung and renal cancers, various types of sarcomas, or hematological malignancies.