In the 2000s, newer generations of drugs appeared on the market called drugs of targeted therapy (TT) drugs. The introduction of TT in oncology has profoundly changed the prognosis of many cancers but also introduced a wide variety of adverse drugs reactions (ADR), including in particular dermatological adverse drug reactions (DADRs). We investigated the evolutions of the notifications of DADRs of anticancer drugs since 2000s in international pharmacovigilance data. For this purpose, we separated non-targeted therapy and targeted therapy. During the period from 01/01/2000 to 31/12/2017, 1,226,252 ICSRs (8.7%) were related to anticancer drugs, among them concerning anticancer drugs, 192,108 cases (15.6%) contained at least one MedDRA term for “skin and subcutaneous tissue disorders” system organ classes. The DADRs of anticancer drugs are in constant increase on the period 2000 to 2017, from 0.91% to 1.90% of the total ADR of Vigibase®. The number of DADRs drugs in the non-targeted therapies class remained stable during this period, while the DADRs of targeted therapy drugs increased and exceeded those of non-targeted therapy in recent years. Using a disproportionality analysis, we found that targeted therapy drugs are associated with a higher risk of reporting DADRs of the type: dermatitis acneiform, hair color changes, acne, and hyperkeratosis and skin toxicity. While, non-targeted therapy drugs are associated with a higher risk of reporting DADRs of the type: skin hyperpigmentation, nail discoloration, dermatitis exfoliative, Hyperhidrosis and alopecia. TT drugs are used more and more for cancer indications and even beyond. This problematic of DADR will become more and more common and should benefit from specialized support with the organization of a coordinated network of professionals.