Losses of 3p13-p24, 5q12-q23, 8p22-p23, 9p21-p24, 10p13-pter, 18q22-q23, and 21q11.2-q21 (40-60% of tumors); loss of the inactive X and loss (or rearrangement) of Y in 70% of tumors from female and male patients respectively; and gains of 2 to 5 extra copies of 3q21-qter, 5p14-pter, 7p13-p22, 8q13-q24.3, and 11q13-q23, (30-40% of tumors) are the most common chromosome abnormalities in head and neck squamous cell carcinomas (SCCs). SCCs are monoclonal and cell lines derived from separate surgeries in the same patient contain closely related subclones. Analysis of subclones within tumors provides clues to the sequence of karyotypic changes. Chromosome hotspots such as loss of distal 18q and gains affecting 11q13-11q21 are likely to contain genes important in the development and progression of SCC.