<p>The evaluation of chemical transport models, CTMs, is essential for the assessment of their performance regarding the physical and chemical parameterizations used. While regional CTMs have been widely used and evaluated over Europe, their validation over Greece is limited. In this study, we investigate the performance of the LOTOS-EUROS v2.2.001 regional chemical transport model in simulating nitrogen dioxide, NO<sub>2</sub>, over Greece from June to December 2018. In-situ NO<sub>2</sub> measurements obtained from the National Air Pollution Monitoring Network are compared with surface simulations over the two major cities of Greece, Athens and Thessaloniki. The model reproduces well the spatial variability of the measured NO<sub>2</sub> with a spatial correlation coefficient of 0.85 for the period between June and December 2018. About half of the 14 air quality monitoring stations show a good temporal correlation to the simulations, higher than 0.6, during daytime (12–15 p.m. local time), while the corresponding biases are negative. Most stations show stronger negative biases during winter than in summer. Furthermore, the simulated tropospheric NO<sub>2</sub> columns are evaluated against ground-based MAX-DOAS NO<sub>2</sub> measurements and space-borne Sentinel 5-Precursor TROPOMI tropospheric NO<sub>2</sub> observations in July and December 2018. LOTOS-EUROS captures better the NO<sub>2</sub> temporal variability in December (0.61 and 0.81) than in July (0.50 and 0.21) when compared to the corresponding measurements of the MAX-DOAS instruments in Thessaloniki and the rural azimuth viewing direction in Athens respectively. The urban azimuth viewing direction in Athens region however shows a better correlation in July than in December (0.41 and 0.19, respectively). LOTOS-EUROS NO<sub>2</sub> columns over Athens and Thessaloniki agree well with the TROPOMI observations showing higher spatial correlation in July (0.95 and 0.82, respectively) than in December (0.82 and 0.66, respectively) while the relative temporal correlations are higher during winter. Overall, the comparison of the simulations with the TROPOMI observations shows a model underestimation in summer and an overestimation in winter both in Athens and Thessaloniki. Updated emissions for the simulations and model improvements when extreme values of boundary layer height are encountered are further suggested.</p>