The European Water Framework Directive (WFD) requires that the ecological status of waterbodies is assessed using multiple biological quality elements (BQEs) that are combined into a single status class. The recommended combination rule (the “one-out, all-out” rule; OOAO) has been criticised for being unreasonably conservative and for being sensitive to uncertainty. In this study, the objective was to compare the sensitivity to uncertainty of four different combination rules: (1) OOAO, (2) OOAO with exclusion of one element, (3) average and (4) weighted average. Index values for 5 BQEs (phytoplankton, phytobenthos, macrophytes, macroinvertebrates and fish) sampled from 10 lakes in the Wel River catchment in Poland were used to classify the lakes according to the OOAO and the three alternative combination rules. Based on the mean and (where possible) standard deviation of these index values, we modelled the risk of misclassification by simulating 10,000 resamples for each BQEs in each lake, classifying each resample and calculating the proportion of misclassified resamples under each combination rule. For individual BQEs, the risk of misclassification increased both with higher uncertainty (standard deviation) and with the proximity of the index value to a class boundary. Under the OOAO rule, the risk of misclassification was more biased towards worse status (“underclassification”) than towards better status. Furthermore, risk of underclassification was more affected by uncertainty under the OOAO rule compared with the alternative combination rules. This analysis has demonstrated the weaknesses associated with the OOAO rule for integration of BQEs for lake classification. However, the alternative combination rules are associated with other shortcomings, such as the need for subjective judgement, and involve a higher risk of not protecting the most sensitive BQE and thus the whole ecosystem. We recommend that future versions of instructions for WFD implementation consider alternatives to the OOAO combination rule, and provide guidelines for weighting of individual BQEs.