The common risk factors for oral and oropharyngeal cancer are tobacco smoking and alcohol consumption, and recently the human papillomavirus (HPV) was shown to be involved in a subgroup. HPV-positive and -negative carcinomas can be distinguished on basis of their genetic profiles. Aim of this study was to investigate patterns of chromosomal aberrations of HPV-negative oral and oropharyngeal squamous cell carcinomas (OOSCC) in order to improve stratification of patients regarding outcome. Thirty-nine OOSCCs were classified on basis of their genetic pattern determined by array comparative genomic hybridization (aCGH). Resulting groups were related to patient and tumor characteristics using the Fisher’s exact test and in addition to survival with the Kaplan–Meier and log rank tests. Classification distinguished three groups, one characterized by hardly any chromosomal aberration (N = 8) and another by a relatively high level (N = 26), and one with a very high level (N = 5) of chromosomal aberrations. This classification was significantly (p = 0.003) associated with survival, with the best survival in the genetically ‘silent’ group and the worst survival in the most aberrant group. The silent profile was significantly (p < 0.05) associated with wild-type TP53, an absence of alcohol consumption and a female gender. These carcinomas were negative for microsatellite instability. This classification of OOSCC was confirmed in an independent set of 89 oral carcinomas. In conclusion, the discovery of these new classes of oral and oropharyngeal cancer with unique genetic and clinical characteristics has important consequences for future basic and clinical studies.