Directive 2010/63/EU (henceforth "Directive") on the protection of animals used for scientific purposes mandates that every project proposal in EU member states involving procedures on living non-human vertebrates and cephalopods has to be approved in an review process, including a harm-benefit-analysis (HBA), to assess "whether the harm to the animals in terms of suffering, pain and distress is justified by the expected outcome taking into account ethical consideration and may ultimately benefit human beings, animals or the environment". Despite the justifying relevance of "outcome" and "benefit", it remains unclear how to understand these concepts. However, national authorities and applicants require a clear understanding of this to carry out a HBA. To analyze the underlying premises of the HBA and its consequences for the evaluation process, we introduce a heuristic to analyze the relation between "outcome", "benefit" and "prospective benefit assessment". We then apply the heuristic to all seven legitimate purposes for animal research stated in the Directive, namely basic research, translational or applied research, product safety, education and training, protection of the environment, preservation of species and forensic inquiries. As we show, regardless of which purpose is aimed for, applicants are hard-pressed to demonstrate tangible benefits in a prospective assessment. In the HBA, this becomes a problem since-as we argue-the only reasonable, expected and tangible outcome of research can ever be knowledge. The potential long-term benefits on the basis of gained knowledge are unforeseeable and impossible to predict. Research is bound to fall short of these proclaimed societal benefits and its credibility will suffer as long as research has to validate itself through short-term societal benefit. We propose to revise the ethical evaluation based on the HBA and we think it necessary to develop an alternative model for project evaluation that focuses on the value of knowledge as a scientific outcome as a necessary but not sufficient condition for societal benefit.