Introduction: Approximately 50% of chronic urticaria cases do not respond adequately to conventional doses of antihistamines, so a number of other therapeutic options have been suggested. Among these, omalizumab is an innovative tool, which now has high-quality evidence that supports its use in difficult cases, rapidly improving the symptom index and the use of medications with a good safety profile.Objective: To report three cases of adult women with spontaneous chronic urticaria with an evolution of more than eight years, which did not improve with high doses of antihistamines and leukotriene receptor blockers, associated with immunomodulatory therapy in which several etiologic mechanisms were combined: chronic spontaneous urticaria with autoimmune and pressure components, and vasculitis.Materials and methods: We report the cases with their clinical and laboratory evaluations, used medication, the response after the start of omalizumab and we performed a review of the literature on the use of this drug in chronic urticaria.Results: In all the presented cases, we obtained complete improvement of symptoms after starting omalizumab.Conclusion: Omalizumab is a successful treatment option in cases of difficult to control chronic urticaria with associated vasculitis in which the options proposed by international guidelines have been exhausted.doi: http://dx.doi.org/10.7705/biomedica.v33i4.782