Background and aim Familial chylomicronemia syndrome (FCS) is a rare autosomal recessive metabolic disorder caused by mutations in genes involved in chylomicron metabolism. On the other hand, multifactorial chylomicronemia syndrome (MCS) is a polygenic disorder and the most frequent cause of chylomicronemia, which results from the presence of multiple genetic variants related to chylomicron metabolism, in addition to secondary factors. However, their clinical, paraclinical, and molecular features are not well established in our country. The objective of this study was to describe the development and results of a screening program for severe hypertriglyceridemia in Colombia. Methods A cross-sectional study was performed. All patients aged > 18 years with triglyceride levels ≥ 500 mg/dL from 2010 to 2020 were included. The program was developed in three stages: 1. Review of electronic records and identification of suspected cases, based on laboratory findings (triglyceride levels ≥ 500 mg/dL); 2. Identification of suspected cases, based on laboratory findings that had no relevant secondary factors; 3. Probable cases were identified as having an FCS score ≥ 8 and performing genetic tests in probable cases with available samples. Results In total, we categorized 2415 patients as suspected clinical cases with a mean age of 53 years, of which 68% corresponded to male patients. The mean triglyceride levels were 705.37 mg/dL (standard deviation [SD] 335.9 mg/dL). After applying the FCS score, 2.4% of patients met the probable case definition, of which only 18 accepted molecular test. Additionally, 7 patients had unique variants in the APOA5 gene (c.694T > C; p.Ser232Pro) or in the GPIHBP1 gene (c.523G > C; p.Gly175Arg), for an apparent prevalence of familial chylomicronemia in the consulting population of 1,2 per 100.000 patients with TG measurement. No previously reported pathogenic variants were detected. Conclusion This study describes a screening program for the detection of severe hypertriglyceridemia. Although we identified seven patients as carriers of a variant in the APOA5 gene, we diagnosed only one patient with FCS. We believe that more programs of these characteristics should be developed in our region, given the importance of early detection of this metabolic disorder.