Background: The human retrosplenial cortex (RSC) is the cortical region of the parietal lobe that lies directly behind the splenium of the corpus callosum. While recent fundamental research in animal models has suggested a very important role for the RSC in orientation, relatively few human cases of lesion to the RSC have been reported in the literature. Furthermore, those few cases have pointed at, in addition to the aforementioned role of this cortical structure in topographical orientation, a potential for other supplementary roles in higher-order cognitive functions such as memory processing and language. Cases presentation: In this article, we report two remarkably asymptomatic cases of extensive oncological lesions to the RSC in otherwise healthy patients younger than 35 years old. We report their surgical treatments and their release from our hospital. During the entire follow-up, patients never reported any issue with topographical orientation or language, which is remarkable compared to cases previously reported. Discussion and conclusions: We then discuss the available clinical literature about RSC lesions in human brain and the possible reasons for such a diversity of reported symptoms, or lack thereof, between cases for a seemingly similar radiological entity. Our cases reveal that understanding of the RSC and its lesions remain scarce and needs to be further investigated, both fundamentally and clinically.