The integration sites of human papillomavirus (HPV) DNA within the cervical carcinoma cell line C4-I and a primary cervical tumor were mapped by in situ hybridization. Cloned cellular sequences flanking the integrated viral DNA were used as probes. For the cell line, the viral integration site was mapped to chromosome region 8q21-q22.3, while in the primary tumor chromosome band 3p21 was the target for integration. The HPV DNA integration appears to occur in the vicinity of fragile sites, oncogenes, and chromosome breakpoints that are characteristic of hematologic malignancies and solid tumors. The integration of HPV may thus promote chromosome changes in cancer cells.