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However, the underlying genetic cause for the development of multiple primary tumors is largely unknown. In the study, we report a rare case with four synchronous distinct histological cancer types in a 26\u2009years old Chinese female. In the patient, whole\u2010exome sequencing identified a homozygous germline insertion mutation in <jats:italic>WWOX<\/jats:italic> which encodes the DNA repair\u2010related enzyme, WW domain containing oxidoreductase. The mutation was found in a heterozygous state in her parents and brother without any cancer phenotype thus far. Surprisingly, we found multiple novel aberrant <jats:italic>WWOX<\/jats:italic> transcripts in the patient's normal colon tissue. The patient's colon metastasis from clear cell adenocarcinoma of the ovary showed a nonhypermutated profile enriched for C\u2010T transition, and harbored somatic pathogenic mutations of <jats:italic>HRAS<\/jats:italic>, <jats:italic>BRCA2<\/jats:italic>, <jats:italic>SMAD4<\/jats:italic>, <jats:italic>CHEK2<\/jats:italic>, and <jats:italic>AKT1<\/jats:italic> genes. To our knowledge, this is the first study reporting <jats:italic>WWOX<\/jats:italic> gene aberrations in a young patient with the early occurrence of multiple primary tumors. \u00a9 2019 Pathological Society of Great Britain and Ireland. 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