Considering that this class of drugs is relatively recent in the clinical oncology practice and that there is still very limited information in the real-world setting about the toxicity profile of these agents, the present pharmacovigilance study aims to analyze two of the most suspected hematological adverse drug reactions (ADRs)—leukopenia and thrombocytopenia—reported in the European EudraVigilance (EV) database associated to CDK4/6 inhibitors—palbociclib, ribociclib and abemaciclib. This evidence concerns the gene CDK4 and Decreased total leukocyte count.