The importance of asymmetric divisions for stem cell function and maintenance is well established in the developing nervous system and the skin; however, its role in gut epithelium and its importance for tumorigenesis is still debated. We demonstrate alignment of mitotic spindles perpendicular to the apical surface specifically in the stem cell compartments of mouse and human intestine and colon. This orientation correlates with the asymmetric retention of label-retaining DNA. Both the preference for perpendicular spindle alignment and asymmetric label retention are lost in precancerous tissue heterozygous for the adenomatous polyposis coli tumor suppressor (Apc). This loss correlates with cell shape changes specifically in the stem cell compartment. Our data suggest that loss of asymmetric division in stem cells might contribute to the oncogenic effect of Apc mutations in gut epithelium.