Purpose: The retrograde intrarenal surgery (RIRS) is a procedure that sees an increase in its use every day and is supported by excellent results in terms of safety and feasibility. We report the first case of fatal mycotic septic complication in a neurological patient for renal stone disease. Case presentation: The case of a woman 44 year-old, with left solitary kidney and history of advanced multiple sclerosis, epilepsy, bedridden and percutaneous endoscopic gastrostomy was described. She was hospitalized for the presence of recurrent lower urinary tract infections. The computed tomography (CT) scan control revealed a 1.7 cm obstructive renal pelvic stone and multiple stones in the bladder. After the refusal of a percutaneous approach, a RIRS was planned and done. No intraoperative complications were observed. In the postoperative period, she developed a urinary sepsis with progressive deterioration of the general conditions. She died 6 days after the RIRS for septic shock with a blood culture positive for Candida glabrata. Discussion: A Pubmed search for fatal complications after RIRS shows only two cases not fully elucidated. Conclusions: The use of flexible ureteroscopes and holmium lasers has a high succes rate; nevertheless, the possibility of a major complication should be kept in mind in order to evaluate all the risk factors, to adopt all the preventive measures for the safety of the patients.