Cerebral cavernous malformations (CCMs) are benign tumours that affect brain capillaries. Although many cases remain asymptomatic, their incidence is steadily increasing. CCMs can arise sporadically or be inherited as autosomal dominant character. Inherited forms result from mutations at three different loci CCM1/KRIT1, CCM2/MGC4607 and CCM3/PDCD10. Etiology of sporadic forms is still unclear. Among the various molecular mechanisms proposed, presence of somatic mutations was sometimes proven. Here we report results obtained by a molecular screening of the three CCMs genes, performed on both germ-line and somatic DNA, isolated from CCM endothelial cells, in eight patients affected by sporadic lesions, who undergone surgery. Comparison of germ-line and somatic sequencing data, for each patient, showed no differences. Our results confirm that presence of somatic mutations is not sufficient to explain CCMs onset in patients affected by sporadic forms and with no CCM genes germ-line mutations. Other possible pathogenic mechanisms are also discussed.