A Caucasian 39-year-old male patient with a poorly-differentiated infiltrating epidermoid penile carcinoma with urethral invasion was diagnosed. The patient received concomitant adjuvant chemotherapy with radiotherapy in the palliative setting, which produced painful ulceration of tumour lesions at loco-regional level (Numerical Rate Scale, NRS=9). The patient consented for treatment with direct topical sevoflurane instillations, at initial doses of 1 mL/cm2 of ulcerated area, as per unit protocol. The local use of undiluted sevoflurane achieved a marked reduction of the pain score in both nociceptive and irruptive pains (average NRS=3 immediately post-application). This improvement was corroborated by a decline in total morphine needs, any adverse events associated with major opiates. PGI-I and CGI-I scales were used before and after treatment with topical sevoflurane to assess patient and clinician perceptions of improvement in the quality of life. The pharmacy of our hospital had the responsibility to elaborate pre-loaded syringes with sevoflurane so that the patient was instilled simply and comfortably.