Chronic spontaneous urticaria (CSU) is a chronic inflammatory skin disease characterized by recurrent wheals and/or angioedema and a significant negative impact on quality of life. Omalizumab is an effective therapy for severe, treatment-refractory CSU; however, relapse after treatment discontinuation remains a major clinical challenge. We present the case of a 54-year-old woman with severe CSU treated with omalizumab within the Polish national drug program. The patient achieved complete clinical remission after the first dose in each treatment cycle and maintained full disease control throughout therapy. Mandatory discontinuation consistently led to rapid and severe relapses. So far, seven consecutive treatment cycles were required, each resulting in prompt remission without loss of efficacy or safety concerns. This case underscores the problem of multiple relapses after mandatory discontinuation of omalizumab treatment, highlighting the need for individualized long-term management and optimized discontinuation strategies.