By applying a training/validation strategy on a cohort of 140 CLL, largely enriched for cases with a TP53 disrupted status, we compared a TP53 functional assay, based on the combined evaluation of TP53 protein expression levels by western blotting and of CDKN1A transcript expression levels by qRT-PCR, with the canonical evaluation of TP53 mutational status by direct sequencing. Here, TP53 is linked to B-cell chronic lymphocytic leukemia.