Dietary fat, both in terms of quantity and quality, has been implicated to cancer development, either positively or negatively. The aim of this work was to evaluate whether olive oil or monounsaturated fat intake was associated with the development of cancer. A systematic search of relevant studies, published in English, between 1990 and March 1, 2011, was performed through a computer-assisted literature tool (i.e., Pubmed). In total 38 studies were initially allocated; of them 19 case-control studies were finally studied (13800 cancer patients and 23340 controls were included). Random effects meta-analysis was applied in order to evaluate the research hypothesis. It was found that compared with the lowest, the highest category of olive oil consumption was associated with lower odds of having any type of cancer (log odds ratio = -0.41, 95%CI -0.53, -0.29, Cohran's Q = 47.52, p = 0.0002, I-sq = 62%); the latter was irrespective of the country of origin (Mediterranean or non-Mediterranean). Moreover, olive oil consumption was associated with lower odds of developing breast cancer (logOR = -0,45 95%CI -0.78 to -0.12), and a cancer of the digestive system (logOR = -0,36 95%CI -0.50 to -0.21), compared with the lowest intake. The strength and consistency of the findings states a hypothesis about the protective role of olive oil intake on cancer risk. However, it is still unclear whether olive oil's monounsaturated fatty acid content or its antioxidant components are responsible for its beneficial effects.