In this review, we describe molecular pathology testing to predict response to targeted treatment of solid tumors, focusing on Italian routine clinical practice. The combination of the universal health care system organized at national, regional, and local levels has led a decentralized model, with a large number of local laboratories performing in-house molecular testing following guidelines issued and external quality assessment organized by the Italian Society of Pathology and Cytopathology-Italian Division of the International Academy of Pathology. In this framework, in the early days of predictive testing, sponsored informatics platforms support to set up national programs that aimed to integrate the activity of oncologists and pathologists to test cancer patients for druggable alterations. More recently, reimbursement for molecular testing is being covered completely by the Italian National Health Service. In the near future, considering the development of complex technologies, we expect that outsourcing samples to next-generation sequencing referral laboratories will take place.