Due to the rarity of the condition, Valentino's syndrome is an underrated differential diagnosis for acute appendicitis. We describe a patient with Valentino's syndrome in whom preoperative and intraoperative diagnoses were challenging due to misleading clinical, investigative, and morphological findings. A 31-year-old woman who was on methylprednisolone for sensory radiculopathy presented to the emergency department with acute right lower quadrant pain. The clinical diagnosis of acute appendicitis was supported by the elevated inflammatory markers and ultrasonographic findings. An appendicectomy and an ovarian cystectomy were performed due to the findings of mild appendicitis and right ovarian endometrioma, respectively. Postoperatively, she developed peritonitis with a purulent bile-stained discharge from the surgical site and per vagina. Contrast-enhanced computed tomography of the abdomen showed a retroperitoneal collection at the second lumbar vertebral level extending along the right paracolic gutter to the pelvis and intraperitoneal fluid collections in right lower quadrant and pelvis. An emergency exploratory laparotomy confirmed a perforation at the posterior aspect of the duodenum which was repaired with an omental patch. Unfortunately, relaparotomy and end ileostomy were required due to colonic perforation with the eroded drain tube. She made an uneventful recovery with intensive care and underwent ileostomy reversal after 12 weeks. We emphasize the clues to have a high degree of suspicion during preoperative and intraoperative evaluation to recognize this lethal mimicker of acute appendicitis.