Background <p>Apolipoprotein E (APO E), a member of the apolipoprotein family, plays a crucial role in lipid metabolism. The association between dyslipidaemia and breast cancer remains inconclusive, and the relationship between APO E gene variants and breast cancer is not well established. This study aimed to determine the distribution of APO E gene variants and assess dyslipidaemia as cardiovascular disease risk factor among Ghanaian breast cancer patients.</p> Methods <p>A case-control approach was used, involving 140 participants comprising 70 breast cancer patients and 70 age-matched non-cancer individuals. Socio-demographic and clinicopathological data were collected using a structured questionnaire. Polymerase chain reaction-restriction fragment length polymorphism analysis was performed on the extracted DNA to determine APO E variants. Serum lipid profiles were assessed using an automated chemistry analyser, and serum lipids indices as cardiovascular diseases risk factors including atherogenic index of plasma were calculated. STATA version 19.0 was used for statistical analysis.</p> Results <p>The APO E3/E4 variant was significantly associated with breast cancer (OR = 2.9; <i>p</i> &lt; 0.001). Breast cancer patients showed elevated levels of triglycerides (TG), total cholesterol (TC), and low-density lipoprotein cholesterol (LDL-c), while high-density lipoprotein cholesterol (HDL-c) levels were lower, suggesting a higher risk of cardiovascular diseases among breast cancer patients compared to the control group (<i>p</i> &lt; 0.001). Also, MDA levels were found to be significantly lower among breast cancer patients compared to the healthy control group (<i>p</i> &lt; 0.01).</p> Conclusion <p>APO E, E3/E4 variant was associated with breast cancer and may contribute to the increased cardiovascular disease risk among the breast cancer patients.</p>