Introduction: Peripheral neurotoxicity and neuropathic pain are well-known complications of several anti-cancer chemotherapeutic agents. Such pain might cause an impairment of the patient's quality of life and is a common limiting factor of anti-cancer chemotherapy. Neurotoxicity in orofacial structures has been previously described as diffuse jaw pain or numbness. Currently, localized pulpal pain is not listed as a possible complication of cytotoxic therapy. The aim of this report was to suggest cytotoxic-induced neurotoxicity as a differential diagnosis for toothache during anti-cancer therapy. Methods: We described the diagnostic process in a patient suffering from severe pulpal pain in apparently intact teeth during cytotoxic therapy. A non-Hodgkin's lymphoma patient complained of 2 episodes of excruciating dental pain evoked by mouth breathing, which caused nocturnal awakenings. Results: Both episodes developed immediately after administrations of cyclophosphamide as part of an anti-cancer chemotherapy protocol. Clinical parameters and radiographic characteristics eliminated other possible dental and facial etiologies. Pulp extirpation (pulpectomy) resulted in immediate pain relief. In both episodes, cytologic evaluation of the extirpated pulp tissue failed to show inflammation or an infiltration of lymphoma cells. Conclusions: This case presented a circumstantial relation between the clinical presentation of dental pain, with associated significant impairment of the patient's quality of life, and the timing of administrations of high-dose cyclophosphamide. It suggests that chemotherapy-induced toxicity might manifest as pulpitis-like toothache, which might present a diaanostic challenae for the dental oractitioner.