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Anticancer treatment with the human epidermal growth factor receptor (HER) 2 inhibitors can lead to significant myocardial dysfunction. The primary aim of the study was to estimate the possible association between gene expression in the ErbB signaling pathway and selected clinical event data in patients with acute heart failure. Twenty-four patients (19 males), aged 68.6 ± 12.3 years, were diagnosed and treated due to acute heart failure. The globaltest method was used for the correlation between blood nuclear cells' gene expression in the ErbB pathway (KEGG pathway id 04012) and important clinical data. Decreased expression of ErbB2/HER2 was found to be associated with the release of troponin and the need for inotropic support, whereas decreased neuregulin 1 (NRG1) expression was found to be associated with a decrease of ejection fraction below 40 % (globaltest p-value < 0.05). In summary, the ErbB signaling pathway and, especially, HER2/ErbB2 receptor expression are significantly associated with some of the recognized, clinically significant parameters of patients with acute heart failure. Evaluation of the molecular function of the HER2 receptor may be essential for the prognosis and targeted therapy of heart diseases.