Abstract Background Cutaneous mastocytosis is a rare pathology characterized by an abnormal proliferation and degranulation of mast cells, affecting the skin. Here we present the case of a patient suffering from chronic resistant mastocytosis. An original integrative method of evaluation was tested in this patient, to improve therapeutic management. It integrated the interactions between stressful life events and medical history as well as psychobehavioral components and neurobiological factors. Case presentation The patient was a 65-year-old Caucasian woman. The cutaneous symptoms of mastocytosis had progressively evolved over the past 36 years, increasingly affecting the patient’s quality of life. At the time of the evaluation, psoralen and ultraviolet A therapy had reduced pruritus, but very unsightly brown-red maculopapules persisted on the chest, back, and arms. We proposed an integrative diagnosis that combined a semistructured interview, a psychometric assessment with the Millon Behavioral Medicine Diagnostic tool, and the collection of medical data. The medical data were compared with the analysis of the significant events in the patient’s life, to determine the threshold of tolerance to stress beyond which the skin symptoms led to profuse thrusts of pruritus. At the same time, the psychobehavioral profile of the patient was determined; this highlighted how social isolation, the denigrated coping style, and problematic compliance could influence the extension of dermatological symptoms. The effects of stressors on the infiltration and degranulation of skin mast cells have been discussed in light of the neurobiological processes currently known. At the end of the evaluation, a new therapeutic strategy was proposed. Conclusion This case report reveals the mind–body relationship of a patient suffering from mastocytosis. It highlights the points of vulnerability and the adaptative strategies specific to each patient to be considered in therapeutic management of other resistant chronic diseases.