Multiple linear regression (MLR) is one of the most commonly used analysitical techniques in nursing research. On the other hand, pre-study sample size calculation is important in almost all types of research. It has been suggested, as a rule of thumb, that when using MLR, 5 cases are needed for each independent variable. It was therefore the aim of this study to examine the validity of the suggested rule. A statistical software was used for the calculation of sample size. Parameters used as inputs to the sample size program included 5% alpha, a population R-squared of 0.1 to 0.9, and numbers of independent variables ranging from 2 to 30. It was found that to achieve a statistical power of at least 80% , 6 to 296 cases would be required for different combinations of parameters. If the median is used as the measure of central tendency, then "on average", 5 cases will be needed for each independent variable. However, the variation was so large that the sample size required for each independent variable could be between 2 and 59; again, depending on the combination of parameters. Nevertheless, the number of additional cases required for each additional independent variable is usually below 5, suggesting that the rule of thumb mentioned above is conservative. In addition to sample size derivation, we also discuss the statistical assumptions involved in the computations, as well as some practical considerations for future reference.