Background and Objective: Nontuberculous mycobacteria (NTM) are common environmental contaminants and, as opportunistic pathogens, they can colonize/infect immunocompromised patients. Our work Aims to report the main features of a cluster of haemodialysis patients infected by Mycobacterium saskatchewanense, and to describe the infection prevention and control (IPC) strategies implemented accordingly. Methods: We conducted a descriptive analysis of data coming from the infectious diseases data stream of the Emilia-Romagna Region. Spectrometric and DNA-sequencing analyses in ultrafiltered liquid were done in the regional reference laboratory, while blood cultures were performed in the local hospital laboratory. Results: Between 04/01/2022 and 18/07/2022, a cluster of 6 patients (3 males and 3 females, median age 63.5 years) with positive blood culture for Mycobacterium saskatchewanense was reported in two HUB hospitals of the Region Emilia-Romagna, Northern Italy. All patients underwent online haemodiafiltration before the symptom’s onset; water samples from the dialysis machines’ ultrafilters also tested positive. The key clinical features reported were varied, including weight loss, asthenia, gastrointestinal symptoms, cough, night sweats, recurrent fever of unknown origin. In addition, common Findings were cytopenia, increased blood levels of systemic inflammation markers, splenomegaly, osteo-medullary granulomas, and pulmonary pathologic imaging. Conclusions: The application of the best IPC strategies (clinical and environmental surveillance, switch to traditional haemodialysis and heat disinfection...) is currently supervised by a regional interdisciplinary team, and preliminary data indicate positive outcomes. As a precaution, considering the extreme fragility of haemodialysis patients, a constant epidemiological monitoring based on clinical and diagnostic criteria is still in place, and regular environmental sampling is being performed.