Treatment guidelines recommend omega-3 with Docosahexaenoic Acid (DHA) and Eicosapentaenoic Acid (EPA) content not above 85% in patients with high plasma levels of triglycerides. Since the different up to date formulation of omega-3 available in commerce must be similar to clinical efficacy and safety, herein, we report the case a 52-year-old woman who presented clinical inefficacy using Olevia(®) omega-3 treatment. Clinical evaluation excluded the presence of intestinal or systemic diseases able to reduce the drug absorption. Switching the therapy from (Olevia(®)) to an equivalent omega-3 formulation (Esapent(®)), we documented a decrease in her plasma triglycerides levels. In order to evaluate a possible difference between these formulations we performed a single blind in vitro dissolution test using three pills for each formulation of omega-3 (Olevia(®), Esapent® and another one chosen between the several formulations available in commerce: DOC Generic(®)) that revealed a significant difference (>20%) in the dissolution time of three different omega- 3 commercially available drug formulation.