: Infectious proctitis remains an underrecognized entity, although sexually transmitted diseases, especially bacterial infections, exhibit a marked increase in their incidence. : Here, we report a case of a 44-year-old man who presented to the emergency department with lower abdominal and rectal pain, tenesmus, fever and night sweats for the past 6 days. : The computed tomography initially revealed a high suspicion of metastatic rectal cancer. The endoscopic findings showed a 5 cm rectal mass, suggestive of malignancy. The histologic examination showed, however, no signs of malignancy and lacked the classical features of an inflammatory bowel disease, so an infectious proctitis was further suspected. The patient reported to have had unprotected receptive anal intercourse, was tested positive for Treponema pallidum serology and received three doses of intramuscular benzathine penicillin G. A control rectosigmoidoscopy, imaging at 3 months and histological evaluation after antibiotic treatment showed a complete resolution of inflammation. : Syphilitic proctitis may mimic various conditions such as rectal cancer or inflammatory bowel disease and requires a high degree of suspicion. Clinicians need to be aware of infectious proctitis in high-risk populations, while an appropriate thorough medical history may guide the initial diagnostic steps.