ETHNOPHARMACOLOGICAL RELEVANCE: The use of CAM including herbal medicine as the most preferred CAM modality, among cancer patients who are taking prescription medications has shown to be highly prevalent worldwide as well as in several Middle Eastern countries, with a high percentage of the patients do not disclose their CAM use to treating physician. AIM OF THE STUDY: The current study aimed to evaluate the patterns of CAM use among two cohorts of cancer patients in Palestine over a three-year period, and to identify socio-demographic factors that are associated with CAM use. MATERIALS AND METHODS: Across-sectional survey of patients attending outpatient cancer clinics. The method was based on a semi-structured questionnaire. In order to identify safety-related concerns associated with the products listed, a literature search was conducted using different databases (PubMed, Micromedex, AltMedDex, and the Natural Medicine Comprehensive Database). RESULTS: In 472 cancer patients including 372 of the 2011 cohort; and 100 of the 2014 cohort, the overall prevalence of CAM use was 69.5%. CAM users were more likely to be ≤65 years old, village resident, being in the midst of chemotherapy, to have high interest spiritual quest, and to have no other chronic diseases. A significant number of CAM users reported using herbal preparations (98.3%, and 89.6% in the two study cohorts, respectively). In the current study, a total of 40 plant taxa belonging to 23 botanical families were reported by ≥3 cancer patients in the two cohort groups. The top most commonly used plant in the 2011 cohort group was Arum palaestinum (43.5%), while Ephedra foeminea emerged as the top most commonly utilized plant (from 0.0% in 2011 to 55.2% in the 2014 cohort), mainly due to a recent publicizing and portraying of the plant in the local media as an effective cancer herbal remedy. Safety-related concerns were associated with 33 (82.5%) herbs, including herb-drug interactions with altered pharmacokinetics (8, 20% herbs), direct toxic effects (16, 40% herbs), and increased in vitro response of cancer cells to chemotherapy (30, 75% herbs). CONCLUSIONS: CAM use, especially herbal medicine in cancer is highly prevalent in Palestine. This study has demonstrated the role of the media on the emergence of new CAM herbal therapies among cancer patients in Palestine, and discussed its potential implications on patients and for oncologists who are treating them. Some of the most widely used herbal medicines by cancer patients in the present work are known to interact with conventional anticancer drugs. Hence, the disclosure of the use of herbal remedies by patients to health professionals with sufficient training in CAM use is important for the later in order to assess whether there are any possible herbal drug interactions and/or harmful drug reactions.