Colorectal tumors are frequently characterized by heterogeneous H2Bub1 levels. [A] Human rectal cancer biopsies were stained for H2Bub1, and the majority of cancer lesions showed high H2Bub1 levels. However, [B] several cancer lesions were characterized by heterogeneous H2Bub1 staining, as shown for two representative tumors. Scale bar: 100 µm. [C] Publicly available [TCGA] data were analyzed for RNF40-associated survival of CRC patients, indicating that tumors displaying high RNF40 expression show a tendency towards poorer survival. [D] Colorectal tumors of Apc1638N/+ mice were stained for H2Bub1 and RNF40 using IHC [n = 9]. Although areas with low and high H2Bub1 levels were detected within the same tumors, H2Bub1 levels were more variable in a manner independent of RNF40 amounts. Scale bar: 100 µm. [E] The percentage of colorectal cancer lesions [n = 23] with no, positive, or heterogeneous RNF40 and H2Bub1 staining was evaluated in Apc1638N/+ mice [n = 9]. Whereas the majority of tumors were characterized by high RNF40 abundance, H2Bub1 levels were frequently heterogeneous. CRC, colorectal cancer; IHC, immunohistochemistry.