This study compares p16( INK4a) immunohistochemistry (IHC), HPV chromogenic in situ hybridization (ISH), and HPV polymerase chain reaction (PCR) genotyping for detection of HPV infection in basaloid squamous carcinoma (BSCC). A retrospective histopathological analysis of 40 BSCC from a single institution was carried out. p16 IHC, HPV DNA extraction and ISH, and HPV PCR genotyping were performed, and there was excellent agreement between all 3 methods of HPV detection. Analysis of variance yielded no significant differences between the results of the 3 tests ( P = .354) and Pearson product-moment correlation coefficients calculated for each pair of tests demonstrated direct correlation (r = .61 for PCR and IHC, r = .61 for PCR and ISH, and r = 1.00 for ISH and IHC). This supports the use of p16(INK4a) IHC as an initial screening tool for HPV infection in BSCC, while definitive evidence of HPV DNA can be sought subsequently with PCR or CISH.