Bendamustine, an alkylating agent with cytotoxic properties, has been increasingly employed in the treatment of chronic lymphocytic leukemia (CLL) either as a single agent or combination with rituximab. Although rarely reported, they can potentially cause hypersensitivity reactions with serious consequences. The objective of the case report was to offer a safe and effective bendamustine desensitization protocol to patients with a hypersensitivity reaction to this drug. We report a case of a patient with a CLL who developed a type IV hypersensitivity reaction to bendamustine and who was successfully treated by drug desensitization. A 51-year-old man with CLL was started on chemotherapy with bendamustin–rituximab developed a type IV hypersensitivity reaction 3 days later. A desensitization protocol was developed for the second cycle of bendamustine. This protocol was well tolerated, and no hypersensitivity reaction was observed. The desensitization protocol allowed us to continue the treatment, and to achieve a favorable response of the CLL. Patients with a hypersensitivity reaction to bendamustine can safely receive bendamustine by our rapid desensitization protocol.