We describe the case of a 75-year-old woman presenting with spotted fever followed by acute renal failure and septic shock. The infection was caused by Rickettsia typhi, not reported in Calabria district (southern Italy) since World War II. The diagnosis of murine typhus was made 3 days after admission and was based solely on clinical criteria when her worsening condition required a prompt move to the intensive care unit. Therapy with tigecycline was then started immediately and the patient improved dramatically. The diagnosis of murine typhus was confirmed 10 days after admission by immunofluorescence assay. Our case is an example of how the diagnosis of murine typhus is challenging. However, in the case of a disease lacking specific symptoms, clinicians should never forget that, even in geographic areas considered free of flea-borne diseases, the components of the enzootic cycle are present and the diagnosis should never be underestimated.