The dynamic cell–cell communication is essential for tissue homeostasis in normal physiological circumstances and contributes to a diversified tumor microenvironment. Although exosomes are extracellular vesicles that actively participate in cell–cell interaction by shutting cellular components, impacts of tumor exosomes in the context of cancer stemness remain elusive. Here, we expand colorectal cancer stem cells (CRCSCs) as cancer spheroids and demonstrate that the β‐catenin/Tcf‐4‐activated RAB27B expression is required for the secretion of CRCSC exosomes. In an exosomal RNA sequencing analysis, a switch of exosomal RNA species from retrotransposons to microRNAs (miRNAs) is identified upon expanding CRCSCs. miRNA‐146a‐5p (miR‐146a) is the major miRNA in CRCSC exosomes and exosomal miR‐146a promotes stem‐like properties and tumorigenicity by targeting Numb in recipient CRC cells. Among 53 CRC patients, those with abundant exosomal miR‐146a expression in serum exhibits higher miR‐146aHigh/NumbLow CRCSC traits, an increased number of tumor‐filtrating CD66(+) neutrophils and a decreased number of tumor‐infiltrating CD8(+) T cells. Our study elucidates a unique mechanism of tumor exosome‐mediated stemness expansion. What's new? The tumor microenvironment (TME) is composed of heterogeneous tumor cells and host cells interacting with each other to promote disease progression. However, diagnostic and prognostic biomarkers to monitor the cancer stem cells (CSCs)‐host interplay are lacking. Here, the authors explore the role of tumor exosomes in cancer stemness and demonstrate that RAB27B‐assisted secretion of miRNA‐dominant exosomes is one critical feature of CSCs. Importantly, they show that colorectal cancer stem cells release miR‐146a‐loaded oncogenic exosomes for reprogramming non‐CSC cells and demonstrate the clinical relevance of exosomal miR‐146a in predicting the TME of CRC patients.