Schneiderian papilloma of the nose is an unusual neoplasm with the propensity for local tissue destruction, recurrence, and malignant degeneration. Human papilloma virus (HPV) is related to a subset of sinonasal papillomas and has been implicated in the pathogenesis of cancer by interaction with the host p53 protein. Detection of p53 and HPV could be clinically useful as tumor markers for lesions with oncogenic potential. Thirty specimens for p53 were studied and nine (30%) stained positive. HPV was detected in six (20%). In the presence of p53, an odds ratio for carcinoma was 1.19:1, or 19% higher than expected. In the presence of HPV the odds ratio for carcinoma was 11.5:1, or 11.5 times higher than expected. In the presence of HPV an odds ratio for finding an elevated amount of p53 was 2.2:1. The data support the hypothesis that HPV and p53 may interact in a novel manner and elevate the risk for neoplasia.