The lipid phosphatase PTEN which directly antagonizes the PI3K pathway (Maehama and Dixon, 1998) has been found to be rarely mutated in B cell malignancies (Grønbæk et al., 1998; Sakai et al., 1998), however, its expression was found to be reduced or lost in CLL (Leupin et al., 2003). The gene discussed is PIK3CA; the disease is B-cell chronic lymphocytic leukemia.