The aim of this study is to compare the prevalence and intensity of symptoms and problems with functioning between women and men with inoperable lung cancer (LC) during 3 months post-diagnosis. One hundred and fifty-nine patients completed the EORTC QLQ C-30 + LC13 at three time points: close to diagnosis and prior to treatment, and one, and 3 months later. Descriptive cross-sectional analyses and longitudinal analyses using repeated measure ANOVA were conducted. These patients reported many and intense symptoms and problems with functioning. The most salient finding from the cross-sectional analysis was that women reported both more, and more intense problems with emotional functioning close to diagnosis. Statistically significant improvements over time were found in both men and women with regard to emotional functioning, dyspnea, insomnia, cough, pain in arm/shoulder, while physical functioning, fatigue, constipation, dysphagia, peripheral neuropathy and alopecia deteriorated significantly over time. The longitudinal analyses suggest that, with the exception of emotional functioning, gender differences were not only related to biological sex alone, but were also found to be related to other components of the patients’ life situation, such as education, age, civil status and type of LC. Sensitivity to different symptom experiences and responses to those experiences between and within women and men is also necessary in the management of symptoms in patients with inoperable LC.