ObjectiveThe current study is an innovative exploratory investigation, aiming at identifying differences in personality profiles within Fibromyalgia Syndrome (FMS) and Chronic Fatigue Syndrome (CFS) patients.MethodIn total, 344 participants (309 female, 35 male) reported suffering from FMS and/or CFS and consented to participate in the study. Participants were recruited at an Israeli FM/CFS patient meeting held in May 2013, and through an announcement posted on several social networks. Participants were asked to complete a research questionnaire, which included FMS criteria and severity scales, and measures of personality, emotional functioning, positivity, social support and subjective assessment of general health. In total, 204 participants completed the research questionnaire (40.7% attrition rate).ResultsA cluster analysis produced two distinct clusters, which differed significantly on psychological variables, but did not differ on demographic variables or illness severity. As compared to cluster number 2 (N = 107), participants classified into cluster number 1 (N = 97) showed a less adaptive pattern, with higher levels of Harm Avoidance and Alexithymia; higher prevalence of Type D personality; and lower levels of Persistence (PS), Reward dependence (RD), Cooperation, Self-directedness (SD), social support and positivity.ConclusionThe significant pattern of results indicates at least two distinct personality profiles of FM and CFS patients. Findings from this research may help improve the evaluation and treatment of FM and CFS patients, based on each patient’s unique needs, psychological resources and weaknesses, as proposed by the current trend of personalized medicine.