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BRAF-driven colorectal cancer is among the poorest prognosis subtypes of colon cancer. Previous studies suggest that BRAF-mutant serrated cancers frequently exhibit Microsatellite Instability (MSI) and elevated levels of WNT signaling. The loss of tumor-suppressor Smad4in oncogenic BRAF-V600Emouse models promotes rapid serrated tumor development and progression, and SMAD4mutations co-occur in human patient tumors with BRAF-V600Emutations. This study assesses the role of SMAD4 in early-stage serrated tumorigenesis. SMAD4loss promotes microsatellite stable (MSS) serrated tumors in an oncogenic BRAF-V600Econtext, providing a model for MSS serrated cancers. Inactivation of Msh2in these mice accelerated tumor formation, and whole-exome sequencing of both MSS and MSI serrated tumors derived from these mouse models revealed that all serrated tumors developed oncogenic WNT mutations, predominantly in the WNT-effector gene Ctnnb1(β-catenin). Mouse models mimicking the oncogenic β-catenin mutation show that the combination of three oncogenic mutations (Ctnnb1, Braf, and Smad4) are critical to drive rapid serrated dysplasia formation. Re-analysis of human tumor data reveals BRAF-V600Emutations co-occur with oncogenic mutations in both WNT and SMAD4/TGFβ pathways. These findings identify SMAD4 as a critical factor in early-stage serrated cancers and helps broaden the knowledge of this rare but aggressive subset of colorectal cancer.