Forty-five patients with de novo acute myeloid leukemia (AML) and 22 patients with newly-diagnosed non-Hodgkin lymphoma (NHL) were investigated. Tests for antiphospholipid antibodies (APA) included the measurement of anticardiolipin antibodies (aCL) with a solid-phase immunoassay, and the detection of the lupus-like anticoagulant (LA) activity. Fifteen patients with AML (33.3%) and 9 patients with non-Hodgkin lymphoma (40.9%) presented elevated APA at diagnosis, as compared to 3 out of 174 persons of the control group (p < 0.0001). APA titles became normal in all patients responding to treatment, whereas non-responders retained elevated levels. In addition, 2 patients (1 with AML and 1 with NHL) who had normal APA at diagnosis and were either refractory to treatment or in relapse, subsequently developed LA and/or aCL positivity. At presentation, the mean levels of IgG- and IgM-aCL in patients were not significantly different from controls, and concordance between aCL and LA results reached just 12%. With regard to the clinical course, we were not able to detect any statistically significant difference between patients with normal and elevated APA. Pretreatment concentrations of IL-6 and TNF-alpha in AML, and soluble form of the receptor for interleukin-2 (sIL-2r) in NHL were found significantly elevated compared to controls (p < 0.001, p = 0.011 and p = 0.016 respectively). In addition, the levels of these cytokines correlated with IgG-aCL at the different times of laboratory investigations. These results demonstrate that APA may have a role as markers of disease activity and progression in some haematological malignancies.