In this study, typing of human papilloma virus (HPV) was performed in squamous cell carcinomas of the lung (n=26) as well as putative primaries of head and neck (n=21) and female genital tract (n=5) of the same patients, to test whether additional information to discriminate lung primaries from metastases can be gained by a direct comparison of the HPV status in both tumors. In 3 (14.2%) patients with head and neck as well as lung squamous cell carcinoma, an identical HPV subtype could be detected in both tumors suggesting metastatic disease. In 9 (42.9%) cases, discordant HPV status strongly suggested secondary primaries of the lung. In the remaining 9 (42.9%) patients, no HPV was evident in either tumor. In all patients with carcinomas of the cervix uteri an identical HPV subtype was detected in the cervical and in the lung tumor. In conclusion, the results suggest HPV typing, a method routinely used in cervical biopsies for years, as a very useful diagnostic tool to discriminate primary from metastatic squamous cell carcinoma of the lung, which in our cohort in 57.1% of cases allowed for almost definite classification.