Several pharmacological agents are associated with hyperlipidemia. Tamoxifen is an example of a drug-induced increase of serum triglyceride levels. However, there are only scarce reports on how inborn errors in lipid metabolism as well as secondary dyslipidemias, including diabetes mellitus, influence the hypertriglyceridemic effect of tamoxifen. Herein, we describe a case of a breast cancer patient receiving tamoxifen who presented with remarkable hypertriglyceridemia in the context of diabetes mellitus. We also provide a brief review of the relevant literature and discuss the mechanisms underlying the pathogenesis of hypertriglyceridemia related to tamoxifen.