Our aim was to map and compare genomic imbalances in human papillomavirus (HPV)‐positive and ‐negative squamous cell carcinomas of the tonsil. Twenty‐five primary carcinomas were analyzed by comparative genomic hybridization. Fifteen (60%) were found to be HPV‐positive by PCR, and the majority were HPV‐16. There were statistically significant differences in the distribution of DNA gains and losses between the HPV‐positive and ‐negative samples. Eleven of 15 HPV‐positive samples (73%) showed gain on chromosome 3q24‐qter, while only 4/10 (40%) HPV‐negative samples had the same gain (p = 0.049). Furthermore, 4/10 (40%) HPV‐negative samples but no HPV‐positive samples had gain on chromosome 7q11.2‐q22 (p = 0.017). As expected, and similar to previous studies, patients with an HPV‐positive tumor had a statistically significantly better disease‐specific survival than patients with an HPV‐negative tumor (p = 0.002). The most common changes, e.g., gain on 3q or 8q, loss on 11q or 13 and loss on chromosome 7q in HPV‐negative tumors, did not have any influence on prognosis. However the number of cases in each subgroup was limited. © 2003 Wiley‐Liss, Inc.