In the emergency setting, right lower quadrant pain is a common clinical scenario. While acute appendicitis is the most relevant cause, there is a wide differential diagnosis. Valentino syndrome is a rare entity in which gastric or duodenal perforation, usually secondary to peptic ulcer disease, presents clinically with right lower quadrant pain mimicking acute appendicitis. It has its origins in Rudolph Valentino, a famous American actor who died of sepsis following an undiagnosed perforated ulcer after an appendectomy. Nowadays, radiological images play a crucial role in this pathology, historically diagnosed using exploratory laparotomy. Through a clinical case and a review of the literature, we aim to describe the historical evolution of Valentino’s syndrome, illustrate its clinical and radiological characteristics and high-light the increasing role of imaging, particularly computed tomography, in its early prospective diagnosis and in guiding targeted treatment. Finally, it is important to consider this pathology when assessing acute abdominal patients with coexisting pneumoperitoneum and appendicitis.