Up to 20% of patients with cryptogenic ischemic stroke have an occult malignancy at the time of stroke presentation, providing an opportunity for early cancer detection. Despite this significant association, there is currently no consensus in international guidelines on how to systematically screen for malignancy in ischemic stroke patients. This review aims to summarize recent evidence on clinical features and scores, and predictive laboratory tests, that can guide malignancy screening in ischemic stroke patients. Our systemic search included PubMed, MEDLINE and Cochrane databases and yielded a total of 12 studies meeting the inclusion criteria for review. Elevated D-dimer levels and multiple infarcts in different cerebral circulations emerged as key markers. Based on the summarized data, we propose a flowchart for clinical decision-making regarding malignancy screening in patients with ischemic stroke. As the initial steps, we recommend using D-dimers cut-offs and stroke pattern on brain imaging to classify patients according to their risk profile. Based on the identified risk, we recommend a subsequent diagnostic workup addressing the most prevalent cancer types, including gastrointestinal tract, lung adenocarcinoma and gender-related cancer. The clinical implications of early malignancy screening and the need for evidence-based guidelines in cryptogenic stroke are discussed.