The objective of this systematic review was to assess the effectiveness of shark cartilage as a treatment option for cancer patients. Six databases were searched from their inception to August 2010. Only RCTs testing shark cartilage against any control intervention in humans with any type of cancer were considered. The selection of studies, data extraction and validation were performed by one reviewer. For safety and toxicity studies, uncontrolled trials and case studies were excluded. Two RCTs met the inclusion criteria. The methodological quality of studies was high. None of the RCTs suggested that shark cartilage plus conventional treatment lead to a significant reduction in tumour size or improvements in overall survival when compared to placebo and conventional treatment. Current clinical evidence does not support the efficacy of oral shark cartilage in cancer treatment.