Resistance to the effects of rocuronium and other neuromuscular blocking agents (NMBA) has been previously reported, including delayed onset of relaxation, rapid recovery and incomplete paralysis under recommended doses. These conditions have been associated with denervation injury, burns, immobilisation, infections, metabolic disorders, and drug interactions. In this report, we describe the case of a young male without any known pre-disposing factor for NMBA resistance, who failed to attain muscle relaxation with non-depolarising NMBA despite high doses of rocuronium and atracurium during two surgeries for colorectal cancer, several months apart. Investigations for drug failure and genetic testing did not indicate a plausible cause. After chemotherapy and tumour resection, the patient underwent a third surgical procedure under general anaesthesia with normalised NMBA response. Patient's written consent was obtained for publication.