Cranial fasciitis, an unusual fibroproliferative lesion that occurs in the scalp of infants, is considered a posttraumatic reactive process similar to nodular fasciitis. Its pathobiology has not been investigated. Over the last 15 years, we diagnosed cranial fasciitis in six children; in one case, the lesion recurred after 4 years. This lesion and two others showed aberrant, diffuse nuclear reactivity for beta-catenin. One of the lesions with aberrant nuclear beta-catenin occurred in a child with a history of familial adenomatous polyposis (FAP) and a germline frameshift adenomatous polyposis coli (APC) mutation, c.878delG. The other APC allele in this tumor showed an acquired nonsense mutation, c.4132C --> T. Both these mutations lead to translation of a truncated APC protein. The other two cases of cranial fasciitis with aberrant nuclear beta-catenin occurred sporadically. One of these showed a point mutation, c.122C --> T, in exon 3 of CTNNB1. This mutation causes replacement of threonine with isoleucine at codon 41, leading to loss of a phosphorylation site in the beta-catenin protein. The third case with nuclear beta-catenin staining was the single one that showed recurrence. This tumor did not show mutations in exon 3 of CTNNB1 or in exons 8/9/16 of APC. The results of this small study indicate a dysregulation of the Wnt/beta-catenin pathway in a subset of cranial fasciitis, suggesting that this subset is pathobiologically related to desmoid fibromatoses rather than to nodular fasciitis. Occasional cases of cranial fasciitis may be associated with FAP and serve as an early indicator of this disease, information that would be important in the early diagnosis of FAP in patients without a family history of polyposis.