Objective: Magnetoencephalography source imaging (MSI) of interictal epileptiform discharges (IED) is a useful presurgical tool in the evaluation of drug-resistant frontal lobe epilepsy (FLE) patients. Yet, failures in MSI can arise related to artifacts and to interference of background activity. Independent component analysis (ICA) is a popular denoising procedure but its clinical application remains challenging, as the selection of multiple independent components (IC) is controversial, operator dependent, and time consuming. We evaluated whether selecting only one IC of interest based on its similarity with the average IED field improves MSI in FLE. Methods: MSI was performed with the equivalent current dipole (ECD) technique and two distributed magnetic source imaging (dMSI) approaches: minimum norm estimate (MNE) and coherent Maximum Entropy on the Mean (cMEM). MSI accuracy was evaluated under three conditions: (1) ICA of continuous data (Cont_ICA), (2) ICA at the time of IED (IED_ICA), and (3) without ICA (No_ICA). Localization performance was quantitatively measured as actual distance of the source maximum in relation to the focus (Dmin), and spatial dispersion (SD) for dMSI. Results: After ICA, ECD Dmin did not change significantly (p > 0.200). For both dMSI techniques, ICA application worsened the source localization accuracy. We observed a worsening of both MNE Dmin (p < 0.05, consistently) and MNE SD (p < 0.001, consistently) for both ICA approaches. A similar behaviour was observed for cMEM, for which, however, Cont_ICA seemed less detrimental. Conclusion: We demonstrated that a simplified ICA approach selecting one IC of interest in combination with distributed magnetic source imaging can be detrimental. More complex approaches may provide better results but would be rather difficult to apply in real-world clinical setting. In a broader perspective, caution should be taken in applying ICA for source localization of interictal activity. To ensure optimal and useful results, effort should focus on acquiring good quality data, minimizing artifacts, and determining optimal candidacy for MEG, rather than counting on data cleaning techniques.