Background The middle colic artery (MCA) is of crucial importance in abdominal surgery, for laparoscopic or open right and transverse colectomies. Against this background, a high number of reports concerning anatomical variations of the MCA have been published intended to contribute to the improvement of operative techniques for the treatment of colon cancer. Despite this extensive literature, briefly reviewed in the present paper, a course of the MCA posterior to the superior mesenteric vein, called a retromesenteric trajectory, has been related to only once, to the best of our knowledge. Methods A total series of 507 patients included in two prospective trials concerning laparoscopic or open right colectomy for cancer between 2011 and 2017 are reported. The investigation included preoperative or postoperative multidetector-computed tomography angiography. Results We found four (0.79%) cases of retromesenteric MCA. They all underwent meticulous image analysis with mesenteric vessels' road mapping, detailedmorphometry, and surgical validation which revealed that, apart from their course, those cases did not differ significantly from the rest of the series. Conclusion This paper therefore documents the worth-knowing behavior causing considerable confusion for the operating surgeon unaware of the abnormality and shows its concrete impact on patient-tailored surgical practice, in particular for laparoscopic D3 colectomy (including the Buncinated process first^ approach).