Evidence of intratumor heterogeneity was found in a variety of cancers, shown to be composed of subclones with different phenotypes. These subclones are able to establish interactions that are barely understood nowadays and may yield relevant implications for cancer progression. Here, two colorectal cancer cell lines derived from the same patient, one from the primary tumor (SW480) and another from a metastatic site (SW620), established a cooperative interaction when both were injected in zebrafish larvae. This cooperative interaction wasn’t observed in vitro, suggesting that the interactions are being mediated by the tumor microenvironment. Furthermore, genetic downregulation of the host innate immune system allowed a SW480 behavior that was positively correlated with the presence of SW620. This is consistent with the hypothesis that the increased fitness of SW480 is due to an immune modulation performed by SW620. All in all, this work alerts for cooperative interactions between tumor subpopulations that may increase the fitness of the tumor as a whole. Therefore, an “ecologically” driven therapy, disrupting the crosstalk between cooperative subpopulations may be more successful. Additionally, another heterogeneous tumor was constructed using one cancer cell line that elongates telomeres through telomerase overexpression (Tert) and another through ALT mechanism, in order to determine if it’s plausible that tumors present both populations, but later, Tert becomes the dominant one. There was no competition nor cooperation in vitro, where Tert displayed a higher proliferation than ALT cells, thus overtaking them. In vivo results were inconclusive, since Tert wasn’t able to engraft in zebrafish.