The diversity of nanotechnologies and of the governance challenges that their applications raise calls for exploration and learning across different cases. We present an Upstream Oversight Assessment (UOA) of expected benefits and potential harms of nanoparticles made of a synthetic polymer (PLGA) to improve vaccines for farmed salmon. Suggested by Jennifer Kuzma and colleagues, an UOA may help identify and prioritise research needs, and it may support evaluations of the adequacy of relevant existing regulatory frameworks. In this work, the UOA approach is modified and supported with elements from the uncertainty analysis framework developed by Warren Walker and colleagues. Empirically, we draw on relevant available published literature and insights generated in an ongoing nanoparticle salmon vaccine project, in which one of the authors participates. Nanotechnologies have not previously been encountered in the regulatory context of fish vaccines, which in part raises unique challenges due to prospective large scale vaccine use in semi-open aquatic systems. Strengthened through cooperation between ELSA and technology researchers we found the UOA useful for an early mapping of benefits and concerns, and for identifying areas in need of further research prior to a nanoparticle based salmon vaccine is developed and taken into use. We consider our approach to represent one among several complementing initiatives that seek to contribute to early stage evaluations of possible negative side effects, broadly conceived, in order to facilitate a more robust nanotechnology development.