AIM: To study the characteristics of APC (adenomatous polyposis coli) gene germline mutation in Chinese patients with familial adenomatous polyposis (FAP). METHODS: APC gene from 14 FAP families was amplified by polymerase chain reaction (PCR) and underwent direct sequencing to determine the micromutation type. For the samples without micromutation, the large fragment deletion of APC gene was examined by multiplex ligation-dependent probe amplification (MLPA). RESULTS: There were gene micromutations in 9 families with a micromutation detection rate of 64.3% (9/14), including 6 frameshift mutations (66.7%), 1 nonsense mutation (11.1%) and 2 splicing mutations 22.2%). Large fragment deletions were detected by MLPA in 2 families. The total mutation detection rate of micromutations and large fragment deletions was 78.6% (11/14). CONCLUSION: The detection rate of APC gene germline mutation can be improved by direct sequencing combined with MLPA large fragment deletion detection.