Chronic lymphocytic leukemia is an adult-onset leukemia with a heterogeneous clinical behavior. When chronic lymphocytic leukemia cases were divided on the basis of IgVH mutational status, widely differing clinical courses were revealed. Since IgVH sequencing is difficult to perform in a routine diagnostic laboratory, finding a surrogate for IgVH mutational status seems an important priority. In the present study, we proposed the use of Cryptochrome- 1 as a new prognostic marker in early-stage chronic lymphocytic leukemia. Seventy patients (Binet stage A, without treatment) were included in the study. We correlated Cryptochrome-1 mRNA with well established prognostic markers such as IgVH mutations, ZAP70, LPL or CD38 expression and chromosomal abnormalities. High Cryptochrome-1 expression correlated with IgVH unmutated samples. In addition, Cryptochrome-1 was a valuable predictor of disease progression in early stage chronic lymphocytic leukemia, therefore it can be introduced in clinical practice with the advantage of a simplified method of quantification.