OBJECTIVES:  Advanced forms of systemic mastocytosis (advSM) are rare diseases characterized by neoplastic mast cell infiltration of tissues, and shortened survival. AdvSM comprises three subtypes: aggressive SM (ASM), SM with an associated hematologic non-mast cell disease (SM-AHNMD), and mast cell leukemia (MCL). SM patients suffer from many disease-related symptoms; therefore, a content-valid patient-reported outcome (PRO) instrument is important for assessing the efficacy of novel treatments. The research goal was to develop a content-valid PRO questionnaire, the Advanced Systemic Mastocytosis Symptom Assessment Form (advSM-SAF), for use in clinical trials. METHODS:  The most common and relevant symptoms to advSM patients were identified through a literature review, expert input, and patient concept elicitation interviews. These results informed the development of the preliminary advSM-SAF, which is being tested for comprehensibility and comprehensiveness through cognitive debriefing interviews (CDIs) with patients. RESULTS:  Based on detailed clinical and pathologic review of medical reports, 12 advSM patients (SM-AHNMD=6, ASM=3, MCL=3) were included in the study. These patients reported 33 unique disease-related symptoms, the most frequent including vomiting (n=9, 75%), abdominal pain (n=8, 67%), spots on the skin (n=8, 67%), diarrhea (n=7, 58%), nausea (n=7, 58%), tiredness/fatigue (n=7, 58%), itching (n=5, 42%), and flushing (n=4, 33%). Patients most desired improvement in abdominal pain, tiredness/fatigue, and nausea. These results, along with the literature review and expert input, informed the development of the advSM-SAF, a ten-item electronic diary assessing abdominal pain, nausea, spots, itching, flushing, tiredness/fatigue, vomiting, and diarrhea using a 24-hour recall period and an 11-point (rated 0-10) numeric response scale. CDIs evaluating the tool to inform potential modifications are ongoing. CONCLUSIONS:  The advSM-SAF is being developed in accordance with scientific practices and regulatory guidelines. Next steps involve finalization of the advSM-SAF based on the CDIs and its translation into additional languages for psychometric evaluation in multinational clinical trials.