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Intrahepatic cholangiocarcinoma (iCCA) is the second most common primary liver tumor, with a median survival of only 13 months. Surgical resection remains the only curative therapy; however, at first detection, only one-third of patients are at an early enough stage for this approach to be effective, thus rendering early diagnosis as an efficient approach to improving survival. Therefore, the identification of higher-risk patients, whose risk is correlated with genetic and pre-cancerous conditions, and the employment of non-invasive-screening modalities would be appropriate. For several at-risk patients, such as those suffering from primary sclerosing cholangitis or fibropolycystic liver disease, the use of periodic (6–12 months) imaging of the liver by ultrasound (US), magnetic Resonance Imaging (MRI)/cholangiopancreatography (MRCP), or computed tomography (CT) in association with serum CA19-9 measurement has been proposed. For liver cirrhosis patients, it has been proposed that at-risk iCCA patients are monitored in a similar fashion to at-risk HCC patients. The possibility of using Artificial Intelligence models to evaluate higher-risk patients could favor the diagnosis of these entities, although more data are needed to support the practical utility of these applications in the field of screening. For these reasons, it would be appropriate to develop screening programs in the research protocols setting. In fact, the success of these programs reauires patient compliance and multidisciplinary cooperation.