Coffee consumption is ubiquitous, and the age of coffee drinking has been declining worldwide. Drinking coffee has often been discouraged especially for youngsters, due to its association with negative effects, mainly attributed to caffeine. Despite the “bad reputation” related to coffee, it has been increasingly demonstrated that it offers more health benefits than possible negative effects.Findings from epidemiological studies and clinical research indicate that coffee consumption is associated with a significant decrease in the risk of developing many different types of cancer, including breast, melanoma and nonmelanoma skin, kidney, gastric, colorectal, hepatocellular carcinoma, and brain cancers. Studies investigating the etiology of brain tumors and melanomas in large cohorts among different populations have identified an inverse association between coffee consumption and the risk of brain tumors and melanomas.A recent study demonstrated that coffee edible plant-derived exosome-like nanoparticles (CEPDENs) can suppress hepatocellular carcinoma proliferation. Based on the potential therapeutic effects of CEPDENs, we have investigated the effects of CEPDENs obtained from roasted and unroasted coffee beans on glioblastoma, neuroblastoma, and melanoma cells using MTT cell viability and flow-cytometry analyses.Our findings indicated that CEPDENs decrease the cell viability of neural crest-derived neuroblastoma and melanoma cells in a dose-dependent manner. In contrast, CEPDENs are not effective in decreasing the cell viability of aggressive glioblastoma cells even at high concentrations. CEPDENs obtained from unroasted coffee are more effective in decreasing tumor cells’ viability. Cell death of different tumor cells is induced by different mechanisms via roasted and unroasted CEPDENs.