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Recently, several studies have emphasized the role of R&D expenditure in determining Total Factor Productivity (TFP). In this paper it is shown that the relationship between R&D variables and TFP is far from being established. In particular, by using data for the Italian economy, it is found that the estimated effects of R&D variables on TFP crucially depends on: (i) the way in which the production function, used to derive Solow residuals, is defined; (ii) the numbers of maintained hypotheses used to estimate Solow residuals; (iii) the level of aggregation of the data employed in the empirical analysis.