Aberrations of the tumor suppressor gene, the fragile histidine triad gene (FHIT), have been reported in a wide variety of human cancers including cervical carcinoma, oral squamous cell carcinoma (SCC) and oesophageal SCC. This study aimed to examine the integrity of the FHIT gene in cutaneous SCC. Allelic imbalance/loss of heterozygosity (AI/LOH) was examined in 21 histologically confirmed cutaneous SCC at two microsatellite markers, D3S1300 and D3S4103, both of which are located within intron 5 of the FHIT gene. Immunohistochemical analysis of FHIT protein expression was also examined in the cutaneous SCC. Ten of the 16 informative cutaneous SCC samples (63%) displayed AI/LOH at the D3S1300 locus, and 13 of the 17 informative cutaneous SCC samples (76%) displayed AI/LOH at the D3S4103 locus. Nine of the 21 SCC samples were found to be positive for FHIT protein expression, however, a further nine SCC samples showed reduced FHIT expression, and three SCC samples did not express the FHIT protein. No correlation between AI/LOH of the FHIT gene and reduced/absent FHIT expression was detected in the cutaneous SCC samples. Further investigation into the role of the FHIT protein in the epidermis is warranted to determine if the reduced/lost expression of FHIT observed in a subset of the cutaneous SCC is contributing to tumorigenesis.