Background Breast cancer is a malignant condition affecting about 2.1 million women worldwide. Cancer cells have increased the level of cholesterol and facilitate lipid biosynthesis and metabolism. Therefore, there is a need for assessment of serum lipid and its association with breast cancer risks. Methods A comparative cross-sectional study was conducted among women with breast cancer (n=23), benign breast lump (n=68) and apparently healthy control (n=91) at Felege Hiwot Comprehensive Specialized Hospital, from January to May, 2020. A convenient sampling technique and an interviewer-administered questionnaires were used to collect data. Five milliliter of fasting blood sample was collected for lipid level analysis using enzymatic colorimetric method. Data entry and analysis were done using Epi Info version 7 and SPSS version 20. One way ANOVA and logistic regression were the tools used for analysis, and a p-value of <0.05 was considered as statistically significant. Results The mean age of healthy control, benign and malignant breast cancer was 32.51±9.44, 33.34±10.664 and 37.65±14.345 years, respectively. The mean serum value of TG among controls, benign and malignant women was 168.67±41.616, 170.1±59.018 and 211.7±82.924 (p<0.001), respectively. The mean serum concentration of HDL-c was significantly different between the three groups (47.61±9.122, 44.69±14.479 and 38.26±7.442: p=0.004) among controls, benign and malignant, respectively. Low serum HDL-c level was significantly associated with age at parity (AOR=3.353; 95% CI=1.33, 8.436), the habit of drinking alcohol (AOR=2.125; 95% CI=1.065, 4.241) and BMI (AOR=3.555; 95% CI=1.13, 11.184). In addition, BMI (AOR: 4.54; 95% CI: 1.45, 14.21) was statistically associated with high LDL-c level. Conclusion The overall prevalence of dyslipidemia was high in breast cancer patients. Age at first parity, alcohol consumption and BMI were significantly associated with low serum HDL-c level.