BACKGROUND Malignant hyperthermia (MH) and anesthesia-induced rhabdomyolysis (AIR) are rare, yet life-threatening complications that need prompt therapeutic actions and logistic preparedness for treatment success. Both conditions are triggered by general anesthetics, particularly volatiles and depolarizing muscle relaxants. In comparison with MH, which is an inherited pharmacogenomic disease of calcium channel receptor subpopulation and arises only after trigger exposure, AIR has been described mostly in patients with muscular dystrophies. In perioperative settings, rhabdomyolysis is also observed during propofol infusion syndrome, neuroleptic malignant syndrome, and cocaine, heroin, and alcohol intoxication. Despite their diverse etiology, the main clinical manifestations of MH and AIR overlap: a hypermetabolic state, hyperpyrexia, hypercarbia, acute renal failure, and hyperkalemia progressing to cardiac arrest, making the therapeutic approach to the patient extremely difficult. CASE REPORT We present an unenviable and challenging clinical scenario of an obligatory general anesthesia with endotracheal intubation in a patient with difficult airways for breast conserving onco-surgery with simultaneous targeted intraoperative 20 Gy irradiation. The case was complicated even further by coincident suspicious clinical presentation of a mild and self-limited hypercarbia, together with a protracted rhabdomyolysis, without hyperpyrexia. Given the atypical and scarce clinical presentation leading to diagnosis uncertainty of MH or AIR, which was proved only after receiving the genetic results, dantrolene was not administered, and the patient underwent successful supportive treatment. CONCLUSIONS The study points to the diagnostic dilemma - crisis event MH or AIR - and raises issues about possible preoperative preventive measures and treatment options in patients with an uncertain diagnosis.