Bortezomib is a first line therapy in multiple myeloma and skin reactions are common with this drug. However, most of the reactions are generalized and are immune mediated. Less common reactions are seen at the injection site when administered subcutaneously which typically manifests as an erythematous patch. We present a case of 61 year old woman with severe multiple myeloma treated with s.c. bortezomib which lead to an atypical cogwheel injection site reaction. With the second dose, she developed a similar reaction but was milder. Interestingly she had a severe tumor lysis syndrome immediately following the first dose which corresponded with the severity of the skin reaction which was milder after the second dose. This rash was self–limiting and did not require any specific therapy. It remains unclear whether the severity of ISR correlates with tumor burden, as occurs with TLS or it is idiosyncratic. A clinician’s familiarity with possible cutaneous manifestations of the cancer being treated is crucial as new drug reactions can occur with every dose and need to be differentiated from cancer itself.