While neuroleptic malignant syndrome (NMS) is typically characterised by delirium, motor rigidity, fever and dysautonomia, the syndrome is not pathognomonic, and NMS remains a diagnosis of exclusion. Here, we describe the case of a 44-year-old woman, with no relevant psychiatric history, admitted to a nephrology unit due to acute renal failure. After administration of antipsychotics, she presented with mental status alteration, generalised tremor, rigidity and autonomic nervous system dysfunction. Fever and rhabdomyolysis, however, were not prominent, and NMS was not considered initially in the differential diagnosis. The resulting delay in diagnosis, with continued administration of antipsychotics, led to progressive clinical deterioration. Once NMS was considered, however, antipsychotics were withdrawn and the patient was treated with electroconvulsive therapy (ECT), followed by administration of a dopamine receptor agonist, with close to full remission of all symptoms. Importantly, during outpatient follow-up, sustained mild and asymmetric tremor and rigidity was noted, leading to a diagnosis of Parkinson’s disease. While this raises questions regarding differential diagnosis between NMS in Parkinson’s disease, versus worsening of Parkinson’s disease due to antipsychotic treatment, the former is supported by the acute and rapidly progressive onset of exuberant autonomic dysfunction and clouded conscience, after administration of a neuroleptic. Ultimately, a definitive distinction between these two alternatives for diagnosis of the inaugural neurological presentation in this patient is not possible. Nevertheless, we believe this case illustrates that NMS can be easily missed, particularly in atypical cases, delaying appropriate treatment, and that a flexible multimodal treatment approach, involving ECT, should be considered for complex clinical cases. Furthermore, it also underlines the importance of post-NMS follow-up, to investigate underlying neurological or medical disorders, particularly in those patients who do not have a full recovery.