Phosphoinositide 3-kinase (PI3K) inhibitors are a class of antineoplastic agents currently approved for the treatment of multiple hematologic malignancies and breast cancer. These medications have specific molecular targets to limit toxicity; however, cutaneous adverse effects are frequently reported and can require cessation of therapy. Morbilliform, eczematous, psoriasiform, and pityriasis rubra pilaris-like eruptions are most common, though exfoliative dermatitis and Stevens-Johnson syndrome/toxic epidermal necrolysis have also been reported. We highlight two cases of photo-accentuated skin reactions to duvelisib, a p110-d and p110-g isoform inhibitor. Both cases required oral corticosteroids and interruption of therapy for definitive management due to severity. Though one patient was able to later continue on therapy, both patients experienced recurrence with repeat exposure to duvelisib, establishing a notable temporal correlation. Thus, these cases contribute a novel presentation of adverse reactions to PI3K inhibitors to existing literature.