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Aims Current diagnostic criteria for pancreatic serous cystadenocarcinoma (SCC) create a grey zone for tumours that are locally invasive but not yet metastatic. We sought to resolve this ambiguity by defining the clinicopathological features and searching for the malignant potential of this aggressive subset of serous neoplasms.Methods A combined cohort of 25 patients was compiled from a systematic literature review and augmented with two institutional cases.Results Infiltrative growth was a near-universal finding (23/25), often in tumours with a prominent solid architecture. This growth pattern was reflected by frequent local invasion into adjacent organs (40%). The malignant potential of these neoplasms was confirmed by the development of metachronous distant metastases in 28% of patients (median time: 40.5 months) despite their absence at presentation. Our institutional cases highlight the diagnostic value of Ki-67 immunohistochemistry, revealing markedly elevated proliferation indices (5% and 10% in hotspots) that starkly contrast with those of conventional serous cystadenomas (<2%).Conclusion Local invasion in serous neoplasms, especially when combined with a solid architecture and high Ki-67 index, defines a high-risk subset highly suspicious for serous cystadenocarcinoma. This interpretation must be balanced against the generally indolent behaviour of most serous neoplasms, and such cases warrant closer clinical surveillance.