Introduction Platinum compounds are frequently used for the treatment of colorectal cancer as initial chemotherapy. Oxaliplatin is a third-generation platinum used for the treatment of stage III colorectal cancer and is associated with hypersensitivity reactions. The incidence of hypersensitivity reaction is approximately 12%, with 1–2% of patients developing moderate to severe reactions. Case report A 54-year-old male patient with stage III B colon cancer was diagnosed and chemotherapy with oxaliplatin was indicated by the oncology service. Within 20 min of the first cycle of oxaliplatin, he developed dyspnea, laryngeal spam, foreign body sensation in the throat, nausea, and diarrhea; therefore, the infusion of oxaliplatin was suspended, and intramuscular epinephrine was administered and intravenous hydrocortisone along with chlorpheniramine with adequate resolution of symptoms. Management and outcome: Intradermal skin test performed at the concentration of 5 mg/ml (dilution 1:100) was positive. Due to the symptoms presented we decided to perform desensitization to oxaliplatin (total dose: 250 mg) with three bags–12 steps protocol with an initial concentration dose of 1/100 of the total dose in a course of 5.56 h with no hypersensitivity reactions. Discussion Approximately 50% of patients who are exposed to oxaliplatin may have hypersensitivity despite premedication. Desensitization protocol induces tolerance to a drug temporarily and is dependent on continuous exposure.