Portfolio decision analysis often evaluates R&D projects one at a time and uses these evaluations as the basis for profit-maximizing funding decisions. This approach can overlook strategic fit between projects. In theory, it is possible to identify synergies between projects and then fund the set of projects that maximize profit. In practice, the time and attention required to identify all such synergies may be prohibitive. Several analytic strategies are applied to simulated project portfolios with varying characteristics, using a matrix representation of interdependent portfolio elements. The results illustrate the potential impact on portfolio profit accruing from various means of considering synergies. The baseline strategy for comparison is a myopic strategy, in which each project is assessed in isolation. The gold standard is a comprehensive strategy in which all synergies are identified. Intermediate strategies may consider either cost or value synergies explicitly, or may include a speculative factor to account for unidentified potential cost or value synergies between projects. Depending on the environment, minimal efforts, moderate efforts or major efforts to comprehend uncertainty are justified. This suggests a contingent approach to project portfolio decision making. Preliminary recommendations are provided to match efforts to characterize the portfolio with the needs of the situation.