Hypersensitivity reactions to chemotherapy drugs are quite frequent. Desensitization for chemotherapy drugs has become an option to maintain first-line therapy in patients who have suffered such reactions.The objective of this study was to describe our experience in desensitization with antineoplastic agents using a rapid 1-solution protocol.We performed a 3-year prospective observational study recording all patients who were desensitized with this protocol. All patients signed an informed consent. Skin test was performed at concentrations previously described as nonirritant. Desensitization was performed using only 1 solution of the drug prepared following the manufacturer instructions. Most drugs were diluted in a volume of 500 mL. We started infusion at 5 mL/h and increased doses at 15-minute intervals to 10, 25, 50, 75, and 100 mL/h. If no reaction occurred, and if the pharmacokinetics of the drug allowed it, we stepped up to 150, 200, and 250 mL/h.Ninety patients were desensitized to 93 drugs: oxaliplatin (30), carboplatin (16), paclitaxel (19), docetaxel (6), cetuximab (5), rituximab (6), and others (11). A total number of 490 procedures were performed. Sixteen patients (17.77%) presented 26 reactions (5.3%). Most reactions appeared in patients who were desensitized to platins and in patients with severe reactions. All but 3 cycles were completely administrated. No deaths or hospital admissions were recorded.This 1-solution protocol for desensitization has demonstrated to be safe and useful in our study population, especially for mild-to-moderate reactions and nonplatinum drugs. If our results were reproducible in other centers and larger populations, they could contribute to simplifying protocols and making desensitization available for more patients.