We have screened mutations of the β‐catenin gene by using the polymerase chain reaction‐single strand conformation polymorphism (PCR‐SSCP) method in 62 malignant bone and soft‐tissue tumors, including malignant fibrous histiocytomas (MFHs), osteosarcomas, synovial sarcomas, liposarcomas, malignant schwannomas, and other types of tumors, as well as 11 benign tumors. β‐Catenin‐activating missense mutations were found in two malignant tumors. One found in MFH occurred at codon 45 and caused an amino acid substitution from serine (one of the GSK3β‐targeted phosphorylation sites) to phenylalanine. The other, detected in synovial sarcoma at codon 32, resulted in an amino acid change from aspartic acid (located adjacent to the phosphorylation target, serine, encoded by codon 33) to tyrosine. Furthermore, we found accumulation of β‐catenin by western‐blotting analysis in 12 of 19 malignant tumors in which we found no mutation involving exon 3. Our results suggested the possible involvement of β‐catenin activation, by β‐catenin gene mutation or alteration of other factor(s), in the formation and/or progression of various types of bone and soft‐tissue tumors.