Development of cervical carcinomas is strongly associated with presence of human papilloma virus (HPV). Recently we found that young patients with breast cancer had a higher frequency of skewed X inactivation in peripheral blood cells, indicating an effect of X-linked genes on breast cancer development. In this study, we investigated the frequency of skewed X-inactivation pattern in blood and tumor biopsies from patients with cervical cancer. No difference in the frequency of skewed X inactivation in blood was found between 142 patients and 437 age-matched controls. Elderly females have a higher frequency of skewed X inactivation in blood cells than younger females. An age effect was confirmed in this study for blood cells in both patients and controls. A tendency to an age effect was also found in the tumor biopsies. The correlation between X inactivation in blood and biopsies was 0.39 (P<0.001), showing that the X inactivation in biopsies to some degree reflects skewing in blood. Furthermore, of eight patients with a skewing of > or =75% in biopsies, seven patients had a skewing in the same direction in their blood cells (P=0.03). Our results indicate that if X-inactivation analysis is to be used in clonality studies of cervical cancers, it is essential to consider both the age and the X-inactivation pattern in blood cells.